Lateral femoral chondral lesions are more frequent when an anterior cruciate ligament tear is concomitant with a lateral femoral notch sign, but do not progress over time.

BACKGROUND: The lateral femoral notch sign (LFNS) is caused by an impact to the lateral femoral condyle during a pivot shift injury and affects 25% to 33% of patients with an anterior cruciate ligament (ACL) rupture. The primary aim of this study was to compare the incidence of chondral lesions 1year after ACL reconstruction, while taking into consideration preoperative chondral damage, in patients with and without a preoperative LFNS. The primary outcome measure was the presence of chondral lesions involving the lateral femoral condyle, confirmed on magnetic resonance imaging (MRI) using the Outerbridge classification, at 1year postoperative. The secondary outcome measures were bone bruise of the lateral femoral condyle confirmed on MRI, the International Knee Documentation Committee (IKDC), Lysholm and Tegner functional scores taken 1year after surgery. METHODS: Sixty patients were included-30 with preoperative LFNS and 30 without-in a retrospective, comparative study of prospectively collected data on patients operated between August 2018 and December 2020. RESULTS: A lateral femoral chondral lesion 1year after surgery was significantly more common in the group with a preoperative LFNS (37% [n=11] versus 13% [n=4] in the group without a preoperative LFNS, p=0.036). Adjusting the statistical analysis for preoperative body mass index (BMI) did not impact these results (adjusted odds ratio [OR]=3.83 [95%CI: 1.03-14.24]; p=0.045). Adjusting for a preoperative lateral femoral chondral lesion had an impact on these results (adjusted OR=0.78 [95%CI: 0.12-5.08]; p=0.793). This indicates that a preoperative LFNS is not significantly and independently associated with a lateral femoral chondral lesion at 1year postoperative when the analysis is adjusted for a preoperative lateral femoral chondral lesion. However, having a preoperative lateral femoral chondral lesion is significantly correlated with the presence of a lateral femoral chondral lesion 1year after the surgery (adjusted OR=63.31 [95%CI: 5.94-674.8]; p=0.001). There were no significant differences in terms of bone bruise on MRI (p=1.0), or for the IKDC (p=0.310), Lysholm (p=0.416) and Tegner (p=0.644) functional scores. The LFNS was still present in 21 out of 30 patients (70%) at 1year postoperative. The preoperative LFNS was significantly smaller in the group without a chondral lesion compared to the group with a chondral lesion 1year after the surgery (median=2.30mm [IQR: 1.40; 3.00] versus 3.10mm [IQR: 2.50; 3.40]; p value=0.045). CONCLUSIONS: Patients with a preoperative LFNS are three times more likely to have a chondral lesion in the notch region 1year after surgery. These chondral lesions are concomitant to the injury and do not progress over time. LEVEL OF EVIDENCE: III.

Antibiotic cement-coated rigid locked nails in infected femoral and tibial nonunion. Reoperation rates of commercial versus custom-made nails.

INTRODUCTION: The objective of this study is to assess bone union, infection control, and reoperation rates in a series of patients with infected femoral or tibial nonunion treated with antibiotic-cement-coated rigid nails and to compare the results obtained with custom-made nails versus commercial nails. METHODS: We retrospectively analyzed a series of consecutive patients with infected nonunion of the femur or the tibia treated with antibiotic-cement-coated rigid nails between January 2010 and 2020. We assessed patients' distinctive characteristics, initial injury, type of nail used (custom-made nail with vancomycin or commercial nail with gentamicin), success rate (bone union + infection control), reoperation rate, and failure rate. Comparative analyses were conducted between reoperated and non-reoperated patients regarding the type of nail used. A multivariate regression analysis was performed to assess the risk variables that impacted reoperation rates. RESULTS: We included 54 patients with 22 (40.74%) infected femoral nonunions and 32 (59.25%) tibial nonunions, who were treated with 38 (70.37%) custom-made antibiotic-cement coated nails and 16 (29.62%) commercial nails. Bone union and infection control were achieved in 51 (94.44%) cases. The reoperation rate was 40.74% (n = 22), and the failure rate was 5.55% (n = 3). The use of custom-made nails was associated with a higher risk of reoperation (Odds Ratio 4.71; 95% Confidence Interval 1.10 - 20.17; p = 0.036). CONCLUSION: Antibiotic-cement-coated nails reached a 94.44% success rate. Nails manufactured in the OR coated with vancomycin cement were associated with a higher risk of reoperation than commercial nails loaded with gentamicin cement. LEVEL OF EVIDENCE: III comparative, observational, non-randomized.

Síndrome de embolismo graso en fractura de huesos largos, reporte de caso / Fat embolism syndrome in long bone fractures, case report

Introducción: El síndrome de embolismo graso es una complicación severa, aun-que poco frecuente de trauma grave. Es desencadenado por el paso de partículas de grasa hacia la microcirculación en varios órganos. La tríada característica: lesión pulmonar, hemorragia petequial y disfunción neurológica. Su prevalencia varía se-gún los criterios diagnósticos y la causa desencadenante, dificultando su detección temprana. Presentación del caso: Caso 1. Paciente 22 años, masculino, sufrió accidente automovilístico con fracturas abierta de fémur, tibia y peroné derechos, resueltas quirúrgicamente, a las 5 horas del evento sufre deterioro respiratorio, petequias conjuntivales, torácicas y en extremidades; posteriormente deterioro de concien-cia, estatus epiléptico y síndrome de hiperactividad simpática paroxística. Caso 2. Paciente 29 años, masculino, sufrió volcamiento del vehículo en el que viajaba, sufriendo fracturas cerradas de tibia, peroné y fémur izquierdas, luego de la cirugía traumatológica sufrió deterioro del estado de conciencia, petequias conjuntivales e hipoxemia.Diagnósticos e intervenciones: los dos pacientes fueron operados para resolución traumatológica dentro de las primeras 24 horas, luego del aparecimiento de síntomas neurológicos se sometieron a neuroimagen encontrándose el patrón de "campo de es-trellas" y recibieron corticoides.Resultados: Caso 1 el desenlace fue estado vegetativo, Caso 2 recuperación completa.Conclusión: La detección es imprescindible para establecer el tratamiento temprano, planificar la cirugía traumatológica o diferirla y estimar el pronóstico según la evolu-ción. El síndrome de embolia grasa cerebral es una causa rara del síndrome de hipe-ractividad simpática paroxística

Introduction: Fat embolism syndrome is a severe, although rare complication of major trauma. It is triggered by the passage of fat particles into the microcirculation in various organs. The characteristic triad: lung injury, petechial hemorrhage and neurological dysfunction. Its prevalence varies according to the diagnostic criteria and the triggering cause, making its early detection difficult. Case presentation: Case 1. Patient 22 years old, male, suffered a car accident with open fracture of the right femur, tibia and fibula, surgically resolved, 5 hours after the event he suffered respiratory impairment, conjunctival, thoracic and extre-mity petechiae; later impaired consciousness, status epilepticus and paroxysmal sympathetic hyperactivity syndrome. Case 2. Patient 29 years old, male, suffered overturning of the vehicle in which he was traveling, suffering closed fractures of the left tibia, fibula and femur, after trauma surgery he suffered impaired consciousness, conjunctival petechiae and hypoxemia.Diagnoses and interventions: Both patients underwent surgery for trauma reso-lution within 24 hours, after the appearance of neurological symptoms they un-derwent neuroimaging finding "star field" pattern, both received corticosteroids.Results: Case 1 the outcome was vegetative state, Case 2 complete recovery.Conclusion: Detection is essential to establish early treatment, to plan trauma sur-gery or to defer it and to estimate prognosis according to evolution. Cerebral fat em-bolism syndrome is a rare cause of paroxysmal sympathetic hyperactivity syndrome.

Role of Macrophages and Plasminogen Activator Inhibitor-1 in Delayed Bone Repair Induced by Glucocorticoids in Mice.

Glucocorticoids delay fracture healing and induce osteoporosis. However, the mechanisms by which glucocorticoids delay bone repair have yet to be clarified. Plasminogen activator inhibitor-1 (PAI-1) is the principal inhibitor of plasminogen activators and an adipocytokine that regulates metabolism. We herein investigated the roles of macrophages in glucocorticoid-induced delays in bone repair after femoral bone injury using PAI-1-deficient female mice intraperitoneally administered with dexamethasone (Dex). Dex significantly decreased the number of F4/80-positive macrophages at the damaged site two days after femoral bone injury. It also attenuated bone injury-induced decreases in the number of hematopoietic stem cells in bone marrow in wild-type and PAI-1-deficient mice. PAI-1 deficiency significantly weakened Dex-induced decreases in macrophage number and macrophage colony-stimulating factor (M-CSF) mRNA levels at the damaged site two days after bone injury. It also significantly ameliorated the Dex-induced inhibition of macrophage phagocytosis at the damaged site. In conclusion, we herein demonstrated that Dex decreased the number of macrophages at the damaged site during early bone repair after femoral bone injury partly through PAI-1 and M-CSF in mice.

Reconstruction of Massive Segmental Distal Femoral Metaphyseal Bone Defects After Open Injury: A Study of 20 Patients Managed with Intercalary Gamma-Irradiated Structural Allografts and Autologous Cancellous Grafts.

BACKGROUND: Our aim was to examine the outcome of gamma-irradiated intercalary structural allografts combined with autologous cancellous grafts in treating large metaphyseal bone defects of the distal femur following open injuries. METHODS: We prospectively included 20 consecutive patients with large metaphyseal bone defects of >4 cm located in the region of the distal femur following open injuries treated between 2010 and 2018, with a mean follow-up of 2 years (range, 2 to 10 years). Of these patients,18 were men and 2 were women. The mean age was 39 years (range, 22 to 72 years). The mean length of the bone defects was 10.1 cm (range, 5.5 to 14.5 cm), and all were in the metaphysis of the distal femur. The surgical technique included initial early debridement and external fixation followed by reconstruction of the bone defect using structural allograft combined with autologous cancellous bone graft harvested from the iliac crest and locking plate fixation. Definitive fixation was performed at an average period of 22.5 days (range, 3 to 84 days) after injury. Osseous union, rate of infection, complications, need for secondary procedures, and functional outcome using the Lower Extremity Functional Scale (LEFS) at the final follow-up were assessed. RESULTS: After excluding 1 patient who was lost to follow-up, 19 patients with complete follow-up were available for analysis. Of those, 13 patients (68%) achieved complete union at both ends of the allograft with host bone without any further intervention. Three patients (16%) developed aseptic nonunion of the proximal end of the allograft requiring 1 additional procedure each to achieve union. Four patients (21%) developed a deep surgical site infection. Of those, 1 elderly patient required above-the-knee amputation following uncontrolled diabetes and infection. A second patient required 2 additional procedures, and a third patient needed 4 additional procedures to achieve union. The fourth patient developed infection after achieving union, and the infection subsided after debridement and implant removal. The mean LEFS score for all 19 patients was 55 (range, 41 to 75). CONCLUSIONS: Use of allograft was a reasonable single-stage alternative solution for massive distal femoral bone defects, which united without additional surgery in two-thirds of the patients and without limb-length discrepancy. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Cadera flotante: análisis comparativo de resultados y lesiones asociadas / Floating hip: comparative analysis of outcomes and associated injuries

Objetivo: Describir los tiempos de internación, cirugía y rehabilitación de una serie de pacientes con cadera flotante. El objetivo secundario fue comparar los resultados obtenidos en función de la reinserción laboral con los de pacientes que sufrieron fracturas de pelvis o acetábulo sin fractura femoral asociada. Materiales y Métodos: Estudio descriptivo, retrospectivo y multicéntrico de pacientes con trauma de pelvis y acetábulo de alta energía, divididos en dos grupos de estudio según la presencia de fractura de fémur asociada homolateral (cadera flotante) para su comparación, durante el período comprendido entre enero de 2014 y marzo de 2019. Resultados: Se incluyó a 102 pacientes con trauma de pelvis o acetábulo agrupados en 2 poblaciones según la presencia de cadera flotante (cadera flotante 23; pelvis/acetábulo 79). Las medianas de días de internación [cadera flotante 15,5 (rango 4-193); pelvis/acetábulo 7 (rango 3-31); p = 0,0001] y de la cantidad de cirugías por paciente [cadera flotante 5 (rango 3-8); pelvis/acetábulo 2 (rango 1-4); p = 0,0001] fueron mayores en los pacientes con cadera flotante. Además, la incapacidad laboral temporaria fue más alta (p = 0,00012), sin diferencias significativas en la tasa de recalificación laboral (p = 0,11). Conclusión: La asociación de la lesión cadera flotante aumentó significativamente el tiempo de internación, los procedimientos quirúrgicos necesarios y el tiempo de recuperación según la incapacidad laboral temporaria en pacientes con trauma de pelvis o acetábulo. Nivel de Evidencia: III

Objective: We aim to describe the lengths of hospitalization, surgery, and rehabilitation of a series of patients with floating hip. As a secondary objective, to compare the outcomes obtained in terms of return to work in patients who had suffered fractures of the pelvis or acetabulum without an associated femoral fracture. Materials and Methods: Descriptive, retrospective, and multicenter study of patients with high-energy trauma to the pelvis and acetabulum divided into two study populations according to the presence of associated ipsilateral femur fracture (floating hip) for comparison, during the period January 2014 - March 2019. Results: 102 patients with pelvis and/or acetabulum trauma were included, grouped into 2 populations according to the presence of a float-ing hip (Floating hip: 23 patients; Pelvis/acetabulum: 79 patients). The median days of hospitalization [floating hip: median = 15.5 (range = 4-193); pelvis/acetabulum: 7 (3-31); p = 0.0001] and the number of surgeries per patient [FH: median = 5 (range = 3-8); pelvis/acetabulum: 2 (1-4); p = 0.0001] were higher in patients with floating hip. Additionally, temporary work disability was higher (p = 0.00012), with no significant differences in the rate of job retraining (p = 0.11). Conclusion: Floating hip significantly increased the length of hospitalization, necessary surgical procedures, and recovery times according to temporary work disability in patients with trauma to the pelvis and/or acetabulum. Level of Evidence: III

The influence of M-CSF on fracture healing in a mouse model.

Macrophage colony-stimulating factor 1 (M-CSF) is known to play a critical role during fracture repair e.g. by recruiting stem cells to the fracture site and impacting hard callus formation by stimulating osteoclastogenesis. The aim of this experiment was to study the impact of systemic M-CSF application and its effect on bony healing in a mouse model of femoral osteotomy. Doing so, we studied 61 wild type (wt) mice (18-week-old female C57BL/6) which were divided into three groups: (1) femoral osteotomy, (2) femoral osteotomy + stabilization with external fixator and (3) femoral osteotomy + stabilization with external fixator + systemic M-CSF application. Further, 12 op/op mice underwent femoral osteotomy and served as proof of concept. After being sacrificed at 28 days bony bridging was evaluated ex vivo with µCT, histological and biomechanical testing. Systemic M-CSF application impacted osteoclasts numbers, which were almost as low as found in op/op mice. Regarding callus size, the application of M-CSF in wt mice resulted in significantly larger calluses compared to wt mice without systemic M-CSF treatment. We further observed an anabolic effect of M-CSF application resulting in increased trabecular thickness compared to wt animals without additional M-CSF application. Systemic M-CSF application did not alter biomechanical properties in WT mice. The impact of M-CSF application in a mouse model of femoral osteotomy was oppositional to what we were expecting. While M-CSF application had a distinct anabolic effect on callus size as well as trabecular thickness, this on bottom line did not improve biomechanical properties. We hypothesize that in addition to the well-recognized negative effects of M-CSF on osteoclast numbers this seems to further downstream cause a lack of feedback on osteoblasts. Ultimately, continuous M-CSF application in the absence of co-stimulatory signals (e.g. RANKL) might overstimulate the hematopoietic linage in favor of tissue macrophages instead of osteoclasts.

Heated Tobacco Products Impair Cell Viability, Osteoblastic Differentiation, and Bone Fracture-Healing.

BACKGROUND: The negative impact of cigarette smoking on bone union has been well documented. However, the impact of heated tobacco product (HTP) use on bone fracture-healing remains unclear. The present study investigated the effect of HTPs on preosteoblast viability, osteoblastic differentiation, and fracture-healing and compared the effects with those of conventional combustible cigarettes. METHODS: Cigarette smoke extracts (CSEs) were generated from combustible cigarettes (cCSE) and HTPs (hCSE). CSE concentrations were standardized by assessing optical density. Preosteoblast (MC3T3-E1) cells were incubated with normal medium, cCSE, or hCSE. The cell viability was assessed via MTT assay. After osteoblastic differentiation of CSE-exposed cells, alkaline phosphatase (ALP) activity was assessed. To assess the in vivo effects of CSEs, a femoral midshaft osteotomy was performed in a rat model; thereafter, saline solution, cCSE, or hCSE was injected intraperitoneally, and bone union was assessed on the basis of micro-computed tomography (µCT) and biomechanical analysis 4 weeks later. RESULTS: MC3T3-E1 cell viability was reduced in a time and concentration-dependent manner when treated with either cCSE or hCSE. ALP activity after osteoblastic differentiation of cCSE-treated cells was significantly lower than that of both untreated and hCSE-treated cells (mean and standard deviation, 452.4 ± 48.8 [untreated], 326.2 ± 26.2 [cCSE-treated], and 389.9 ± 26.6 [hCSE-treated] mol/L/min; p = 0.002). Moreover, the levels of osteoblastic differentiation in untreated and hCSE-treated cells differed significantly (p < 0.05). In vivo assessment of the femoral midshaft cortical region revealed that both cCSE and hCSE administration significantly decreased bone mineral content 4 weeks after surgery compared with levels observed in untreated animals (107.0 ± 11.9 [untreated], 94.5 ± 13.0 [cCSE-treated], and 89.0 ± 10.1 mg/cm3 [hCSE-treated]; p = 0.049). Additionally, cCSE and hCSE-exposed femora had significantly lower bone volumes than unexposed femora. Biomechanical analyses showed that both cCSE and hCSE administration significantly decreased femoral maximum load and elastic modulus (p = 0.015 and 0.019). CONCLUSIONS: HTP use impairs cell viability, osteoblastic differentiation, and bone fracture-healing at levels comparable with those associated with combustible cigarette use. CLINICAL RELEVANCE: HTP use negatively affects bone fracture-healing to a degree similar to that of combustible cigarettes. Orthopaedic surgeons should recommend HTP smoking cessation to improve bone union.

Femoral Injury Over the Site of Spontaneous Regression of an Osteochondroma in a Teenage Athlete.

ABSTRACT: The spontaneous regression of an osteochondroma is extremely rare. We report a case of medial femoral condyle impaction fracture over the site of spontaneous regression of a pedunculated osteochondroma discovered on advanced imaging after an acute injury in a 16-year-old male American football athlete. Although spontaneous regression of an osteochondroma has been described, the case presented reveals questions regarding resultant architectural changes to the bone after resorption, leaving it prone to injury. This is the first case that describes increased injury risk potential at the site of osteochondral regression.

Treatment of B1 Distal Periprosthetic Femur Fractures.

The burden of periprosthetic distal femoral fractures is projected to increase accordingly with the increase in total knee arthroplasties (TKAs) performed globally in the future. Less invasive plating and intramedullary (IM) nailing techniques still seem to provide similar outcomes based on current literature. Double-plating and combination techniques may prove to be beneficial in the future pending further large-scale studies but currently have not demonstrated superiority over single plating and IM nailing based on current evidence. Distal femoral replacement may provide a useful option for future treatment, provided it is performed by a trained knee arthroplasty surgeon.

The mechanism of pyrroloquinoline quinone influencing the fracture healing process of estrogen-deficient mice by inhibiting oxidative stress.

It is reported that oxidative stress plays a detrimental role in the process of bone fracture healing. And pyrroloquinoline quinone (PQQ) is used as antioxidant. However, there is no report about whether PQQ supplementation can promote fracture healing by eliminating oxidative stress. To investigate the protective effect of PQQ on fracture healing, open mid-diaphyseal femur fractures model were created in sham, ovariectomized (OVX) mice and PQQ-treated OVX mice. Our results confirmed that PQQ played a preventive and protective role in OVX-induced delay of bone fracture healing by inhibiting oxidative stress, subsequently promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption. The findings of this study not only revealed the mechanism of PQQ supplementation in promoting fracture healing, but also provide experimental and theoretical basis for the clinical application of PQQ in the treatment of bone fracture.

Vascular Endothelial Growth Factor and Mesenchymal Stem Cells Revealed Similar Bone Formation to Allograft in a Sheep Model.

INTRODUCTION: Mesenchymal stem cells (MSCs) and vascular endothelial growth factor (VEGF) are key factors in bone regeneration. Further stimulation should establish an enhanced cell environment optimal for vessel evolvement and hereby being able to attract bone-forming cells. The aim of this study was to generate new bone by using MSCs and VEGF, being able to stimulate growth equal to allograft. METHODS: Eight Texel/Gotland sheep had four titanium implants in a size of 10 × 12 mm inserted into bilateral distal femurs, containing a 2 mm gap. In the gap, autologous 3 × 106 MSCs seeded on hydroxyapatite (HA) granules in combination with 10 ng, 100 ng, and 500 ng VEGF release/day were added. After 12 weeks, the implant-bone blocks were harvested, embedded, and sectioned for histomorphometric analysis. Bone formation and mechanical fixation were evaluated. Blood samples were collected for the determination of bone-related biomarkers and VEGF in serum at weeks 0, 1, 4, 8, and 12. RESULTS: The combination of 3 × 106 MSCs with 10 ng, 100 ng, and 500 ng VEGF release/day exhibited similar amount of bone formation within the gap as allograft (P > 0.05). Moreover, no difference in mechanical fixation was observed between the groups (P > 0.05). Serum biomarkers showed no significant difference compared to baseline (all P > 0.05). CONCLUSION: MSCs and VEGF exhibit significant bone regeneration, and their bone properties equal to allograft, with no systemic increase in osteogenic markers or VEGF with no visible side effects. This study indicates a possible new approach into solving the problem of insufficient allograft, in larger bone defects.

Experimental study on repair of large segmental bone defects of goat femur by nano calcium-deficient hydroxyapatite-multi (amino acid) copolymer membrane tubes.

OBJECTIVE: The purpose of this study was to observe feasibility of nano calcium-deficient hydroxyapatite-multi (amino acid) copolymer (n-CDHA-MAC) membrane tubes in repairing goat femurs' large defects. METHODS: Twelve goats were divided into two groups, whose femurs were created 30 mm segmental bone defects and then implants were performed. In experimental group, the bone defect of right femur was reconstructed by n-CDHA-MAC membrane tube, while left side was reconstructed by allogenic bone tube in control group. Every three goats were sacrificed at 4, 8, 16, 24 weeks after operation respectively. General observation, X-ray analysis, histology, Scanning electron microscope (SEM) examination and protein level comparison of BMP-2 were conducted to evaluate the effects of repairing segmental bone defects. RESULTS: All goats recovered well from anesthesia and surgical interventions. The radiographic evaluations showed that periosteal reaction outside of the membrane tubes and allogenic bone tubes were observed 4 weeks after surgery. At 16 weeks, callus was continuously increased in experimental group, which was more obvious than control group. At 24 weeks, callus outside of the membrane tubes connected together. Histologic evaluation showed fibro-cartilage callus was evolved into bony callus in experimental group, which was more obvious than control group at 8 and 16 weeks. The protein expression level of BMP-2 increased at 4, 8 weeks and peaked at 16 weeks in experimental groups. There were statistical differences at 8 and 16 weeks (P < 0.05). At each time point in 8, 16, 24 weeks after surgery, the bending stiffness, torsional stiffness and compressive strength of the two groups were similar, and there was no significant difference (P > 0.05). CONCLUSIONS: This novel surface degradation n-CDHA-MAC membrane tube has good ability to maintain enough membrane space, which can provide long-term and stable biomechanical support for large bone defects and integrate well with the surrounding bone.

Clinical and radiological assessment of the induced membrane technique using beta-tricalcium phosphate in reconstructive surgery for lower extremity long bone defects.

AIMS: To clarify the effectiveness of the induced membrane technique (IMT) using beta-tricalcium phosphate (ß-TCP) for reconstruction of segmental bone defects by evaluating clinical and radiological outcomes, and the effect of defect size and operated site on surgical outcomes. METHODS: A review of the medical records was conducted of consecutive 35 lower limbs (30 males and five females; median age 46 years (interquartile range (IQR) 40 to 61)) treated with IMT using ß-TCP between 2014 and 2018. Lower Extremity Functional Score (LEFS) was examined preoperatively and at final follow-up to clarify patient-centered outcomes. Bone healing was assessed radiologically, and time from the second stage to bone healing was also evaluated. Patients were divided into ≥ 50 mm and < 50 mm defect groups and into femoral reconstruction, tibial reconstruction, and ankle arthrodesis groups. RESULTS: There were ten and 25 defects in the femur and tibia, respectively. Median LEFS improved significantly from 8 (IQR 1.5 to 19.3) preoperatively to 63.5 (IQR 57 to 73.3) at final follow-up (p < 0.001). Bone healing was achieved in all limbs, and median time from the second stage to bone healing was six months (IQR 5 to 10). Median time to bone healing, preoperative LEFS, or postoperative LEFS did not differ significantly between the defect size groups or among the treatment groups. CONCLUSION: IMT using ß-TCP provided satisfactory clinical and radiological outcomes for segmental bone defects in the lower limbs; surgical outcomes were not influenced by bone defect size or operated part. Cite this article: Bone Joint J 2021;103-B(3):456-461.

Exosomal miR-335 derived from mature dendritic cells enhanced mesenchymal stem cell-mediated bone regeneration of bone defects in athymic rats.

BACKGROUND: Transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) embedded in a bio-compatible matrix has been demonstrated as a promising strategy for the treatment of bone defects. This study was designed to explore the effect and mechanism of exosomes derived from mature dendritic cells (mDC-Exo) on the BM-MSCs-mediated bone regeneration using the matrix support in an athymic rat model of femoral bone defect. METHODS: The BM-MSCs were isolated from rats and incubated with osteoblast induction medium, exosomes derived from immature DCs (imDC-Exo), mDC-Exo, and miR-335-deficient mDC-Exo. BM-MSCs treated without or with mDC-Exo were embedded in a bio-compatible matrix (Orthoss®) and then implanted into the femoral bone defect of athymic rats. RESULTS: mDC-Exo promoted the proliferation and osteogenic differentiation of BM-MSCs by transferring miR-335. Mechanistically, exosomal miR-335 inhibited Hippo signaling by targeting large tongue suppressor kinase 1 (LATS1) and thus promoted the proliferation and osteogenic differentiation of BM-MSCs. Animal experiments showed that mDC-Exo enhanced BM-MSCs-mediated bone regeneration after bone defect, and this effect was abrogated when miR-335 expression was inhibited in mDC-Exo. CONCLUSION: mDC-Exo promoted osteogenic differentiation of BM-MSCs and enhanced BM-MSCs-mediated bone regeneration after femoral bone defect in athymic rats by transferring miR-335.

Role of microRNA-335 carried by bone marrow mesenchymal stem cells-derived extracellular vesicles in bone fracture recovery.

Mesenchymal stem cells (MSCs) have the potential to reduce healing time and treat nonunion in fracture patients. In this study, bone marrow MSCs-derived extracellular vesicles (B-EVs) were firstly extracted and identified. CD9-/- and normal mice were enrolled for the establishment of fracture models and then injected with B-EVs. Osteoblast differentiation and fracture recovery were estimated. The levels of osteoblast-related genes were detected, and differentially expressed microRNAs (miRs) in B-EVs-treated normal fracture mice were screened and verified. The downstream mechanisms of miR were predicted and assessed. The loss-of functions of miR-335 in B-EV and gain-of-functions of VapB were performed in animal and cell experiments to evaluate their roles in bone fracture. Collectively, B-EVs promoted bone fracture recovery and osteoblast differentiation by releasing miR-335. miR-335 downregulation in B-EVs impaired B-EV functions in fracture recovery and osteoblast differentiation. miR-335 could target VapB, and VapB overexpression reversed the effects of B-EVs on osteoblast differentiation. B-EV treatment activated the Wnt/ß-catenin pathway in fracture mice and osteoblasts-like cells. Taken together, the study suggested that B-EVs carry miR-335 to promote bone fracture recovery via VapB and the Wnt/ß-catenin pathway. This study may offer insights into bone fracture treatment.

Risk Assessment for Pathological Fracture After Bone Tumour Biopsy.

AIM: This study aimed to identify the risk of pathological fractures after bone tumour biopsy. MATERIALS AND METHODS: Fifty rabbit femurs were divided into groups according to defect size: Control (no defect), type 1 (10% width), type 2 (20% width), type 3 (30% width), and type 4 (40% width). Another 20 were also divided into control, type A (27% length), type B (40% length), and type C (53% length) groups. Performing femoral head compression testing allowed each parameter (maximum load, displacement, elastic modulus, and fracture energy) to be calculated individually. RESULTS: Compressive maximum load was significantly higher for type 1 than for the other types when testing rectangular defects of different widths, while there were no significant differences between the three types when testing by defect length. CONCLUSION: It may be useful for orthopaedic oncologists to make a rectangular biopsy hole with a width measuring less than 10% of the circumference and to enlarge the hole longitudinally to avoid pathological fracture.

Platelet-derived biomaterials-mediated improvement of bone injury through migratory ability of embryonic fibroblasts: in vitro and in vivo evidence.

Bony injuries lead to compromised skeletal functional ability which further increase in aging population due to decreased bone mineral density. Therefore, we aimed to investigate the therapeutic potential of platelet-derived biomaterials (PDB) against bone injury. Specifically, we assessed the impact of PDB on osteo-inductive characteristics and migration of mouse embryonic fibroblasts (MEFs). Osteogenic lineage, matrix mineralization and cell migration were determined by gene markers (RUNX2, OPN and OCN), alizarin Red S staining, and migration markers (FAK, pFAK and Src) and EMT markers, respectively. The therapeutic impact of TGF-ß1, a key component of PDB, was confirmed by employing inhibitor of TGF-ß receptor I (Ti). Molecular imaging-based in vivo cellular migration in mice was determined by establishing bone injury at right femurs. Results showed that PDB markedly increased expression of osteogenic markers, matrix mineralization, migration and EMT markers, revealing higher osteogenic and migratory potential of PDB-treated MEFs. In vivo cell migration was manifested by expression of migratory factors, SDF-1 and CXCR4. Compared to control, PDB-treated mice exhibited higher bone density and volume. Ti treatment inhibited both migration and osteogenic potential of MEFs, affirming impact of TGF-ß1. Collectively, our study clearly indicated PDB-rescued bone injury through enhancing migratory potential of MEFs and osteogenesis.

Progression of Asymptomatic Contralateral Femur in Patients with Complete Atypical Femoral Fracture, According to Initial Radiographic Findings.

BACKGROUND: Atypical femoral fracture (AFF) is associated with high prevalence rates of prodromal symptoms, bilateral involvement, complications, and the need for prophylactic fixation due to a risk of an impending fracture. Although most complete AFF cases have an asymptomatic contralateral femur at the initial presentation, there is lack of clarity on its progression. We evaluated the radiographic progression of asymptomatic contralateral femora in patients with a complete AFF and investigated the characteristics of these patients. METHODS: The medical records of 80 consecutive patients who had been treated for a complete AFF were retrospectively evaluated. We excluded 14 patients who had been lost to follow-up, 10 whose contralateral femur initially had been symptomatic and had been treated simultaneously, and 3 whose contralateral femur had previously been treated surgically. The remaining 53 patients were all women with an average age of 71.8 years. The average duration of bisphosphonate (BP) use was 63.6 months, and the mean follow-up duration was 48.9 months. All of the contralateral femora were asymptomatic and were divided into 2 grades according to the initial radiographic findings. We evaluated the prevalence of radiographic progression according to the grades and compared patient characteristics between the progression and non-progression groups. RESULTS: Radiographic progression was noted in 18 patients (34%) during the follow-up: 3 (12%) of 25 in grade 1 and 15 (53.6%) of 28 in grade 2 (p < 0.001). The mean time to progression for these 18 patients was 25.6 months, which also differed significantly depending on the grade (p = 0.02). Eleven and 9 (61.1% and 25.7%) of the patients received BP postoperatively in the progression and non-progression groups, respectively (p = 0.01). CONCLUSIONS: The prevalence of radiographic progression was relatively high, even though the contralateral femur was initially asymptomatic, and differed significantly according to the initial radiographic grade. The frequency of postoperative BP use was significantly higher in the progression group. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Low Back Pain Improves After Surgery for Lesser Trochanteric-Ischial Impingement.

PURPOSE: To assess the effects of surgery for lesser trochanteric-ischial impingement (LTI) on low back pain. METHODS: The records of patients with LTI who underwent endoscopic partial resection of the lesser trochanter (LT) between May of 2017 and February of 2019 were reviewed. Inclusion criteria were the presence of low back pain in association with hip pain, diagnosis of LTI, and partial resection of the LT to treat LTI. Exclusion criteria were less than 12 months of postoperative follow-up and hip or spine surgery after the LTI surgery. Patients were assessed before surgery and at the most recent follow-up with the modified Harris Hip Score and Oswestry Disability Index for lumbar spine. RESULTS: Thirty patients (31 hips) met the inclusion criteria. Four patients were lost to follow-up. Two patients with borderline dysplasia and grade 1 and 2 osteoarthritis underwent total hip arthroplasty after the partial resection of the LT. The results are presented considering the remaining 24 patients (25 hips). The average age at surgery was 51 years (range 32-65 years). The mean follow-up after the surgery for LTI was 19 months (range 12-35 months). The mean ± SD ODI improved from 48% ± 15 before the LTI surgery to 21% ± 22 (P < .001) at the most recent follow-up. Improvement in the Oswestry Disability Index above the minimal clinical important difference was observed in 16 patients (67%) following the LTI surgery. The mean ± SD modified Harris Hip Score improved from 55.8 ± 14 before LTI surgery to 81.3 ± 14.3 (P < .001). CONCLUSIONS: Decrease in low back pain above the minimal clinically important difference is observed in 2 of 3 patients after partial resection of the LT. LEVEL OF EVIDENCE: Level IV, therapeutic case series.