Objectives
Exosomes, as important players in intercellular communication due to their ability to transfer certain molecules to target cells, are believed to take similar effects in promoting bone ...regeneration with their derived stem cells. Studies have suggested that umbilical cord mesenchymal stem cells (uMSCs) could promote angiogenesis. This study investigated whether exosomes derived from uMSCs (uMSC‐Exos) could enhance fracture healing as primary factors by promoting angiogenesis.
Materials and Methods
uMSCs were obtained to isolate uMSC‐Exos by ultrafiltration, with exosomes from human embryonic kidney 293 cells (HEK293) and phosphate‐buffered saline (PBS) being used as control groups. NanoSight, laser light scattering spectrometer, transmission electron microscopy and Western blotting were used to identify exosomes. Next, uMSC‐Exos combined with hydrogel were transplanted into the fracture site in a rat model of femoral fracture. Bone healing processes were monitored and evaluated by radiographic methods on days 7, 14, 21 and 31 after surgery; angiogenesis of the fracture sites was assessed by radiographic and histological strategies on post‐operative day 14. In vitro, the expression levels of osteogenesis‐ or angiogenesis‐related genes after being cultured with uMSC‐Exos were identified by qRT‐PCR. The internalization ability of exosomes was determined using the PKH67 assay. Cell cycle analysis, EdU incorporation and immunofluorescence staining, scratch wound assay and tube formation analysis were also used to determine the altered abilities of human umbilical vein endothelial cells (HUVECs) administered with uMSC‐Exos in proliferation, migration and angiogenesis. Finally, to further explore the underlying molecular mechanisms, specific RNA inhibitors or siRNAs were used, and the subsequent effects were observed.
Results
uMSC‐Exos had a diameter of approximately 100 nm, were spherical, meanwhile expressing CD9, CD63 and CD81. Transplantation of uMSC‐Exos markedly enhanced angiogenesis and bone healing processes in a rat model of femoral fracture. In vitro, other than enhancing osteogenic differentiation, uMSC‐Exos increased the expression of vascular endothelial growth factor (VEGF) and hypoxia inducible factor‐1α (HIF‐1α). uMSC‐Exos were taken up by HUVECs and enhanced their proliferation, migration and tube formation. Finally, by using specific RNA inhibitors or siRNAs, it has been confirmed that HIF‐1α played an important role in the uMSC‐Exos‐induced VEGF expression, pro‐angiogenesis and enhanced fracture repair, which may be one of the underlying mechanisms.
Conclusions
These results revealed a novel role of exosomes in uMSC‐mediated therapy and suggested that implanted uMSC‐Exos may represent a crucial clinical strategy to accelerate fracture healing via the promotion of angiogenesis. HIF‐1α played an important role in this process.
Exosomes from human umbilical cord mesenchymal stem cells enhance fracture healing through HIF‐1α‐mediated promotion of angiogenesis in a rat model.
Summary
The risk factors for atypical femur fracture in patients exposed to bisphosphonates for at least 1 year were examined. Prolonged and continuous use of bisphosphonates, long-term use of ...glucocorticoids, and a higher body mass index were associated with increased risk of atypical femur fracture.
Introduction
The purpose of the present study is to determine whether rheumatoid arthritis (RA) and other clinical factors are associated with an increased risk of bisphosphonate (BP)-related atypical femur fracture (AFF).
Methods
A retrospective nested case-control study of patients who had taken BPs for at least 1 year was conducted. Patients with AFF were identified by reviewing surgical and radiographic records. Three controls with no history of AFFs were randomly selected and age- and sex-matched to each patient with AFFs. Cox proportional hazard models were used to analyze the independent contribution of risk factors to BP-related AFF.
Results
Among the 35,104 patients prescribed BPs for at least 1 year, 43 females (mean age, 68 years) suffered AFFs (0.12%). Patients with AFFs were exposed to BPs for a mean of 7.3 years. Patients with AFFs were exposed to BPs for longer than those without AFFs and continued treatment without a drug holiday. More patients with AFF than controls had taken glucocorticoids and disease-modifying anti-rheumatic drugs. Multivariate Cox regression analyses estimated that long-term use of glucocorticoids, prolonged exposure to BP without cessation, and every 1 kg/m
2
increase in the body mass index (BMI) increased the hazard ratio for AFFs by 3.0, 5.2, and 1.2, respectively.
Conclusions
Prolonged and continuous use of BPs, long-term use of glucocorticoids, and a higher BMI increase the risk of AFFs. Switching long-term BP and glucocorticoid users to other bone-protective agents should be considered.
The aim of this retrospective study was to assess the incidence of early periprosthetic femoral fracture (PFF) associated with Charnley-Kerboull (CK) femoral components cemented according to the ...'French paradox' principles through the Hueter anterior approach (HAA) in patients older than 70 years.
From a prospectively collected database, all short CK femoral components implanted consecutively from January 2018 to May 2022 through the HAA in patients older than 70 years were included. Exclusion criteria were age below 70 years, use of cementless femoral component, and approaches other than the HAA. A total of 416 short CK prostheses used by 25 surgeons with various levels of experience were included. All patients had a minimum of one-year follow-up, with a mean of 2.6 years (SD 1.1). The mean age was 77.4 years (70 to 95) and the mean BMI was 25.3 kg/m
(18.4 to 43). Femoral anatomy was classified according to Dorr. The measured parameters included canal flare index, morphological cortical index, canal-calcar ratio, ilium-ischial ratio, and anterior superior iliac spine to greater trochanter (GT) distance.
Among the 416 THAs, two PFFs (0.48% (95% confidence interval 0.13 to 1.74)) were observed, including one Vancouver type B2 fracture 24 days postoperatively and one intraoperative Vancouver type B1 fracture. Valgus malalignment and higher canal bone ratio were found to be associated with PFF.
This study demonstrated that short CK femoral components cemented according to the French paradox were associated with a low rate of early PFF (0.48%) in patients aged over 70 years. Longer follow-up is warranted to further evaluate the rate of fracture that may occur during the bone remodelling process and with time.
This is the second report of an atypical peri-implant femoral fracture occurring at the distal screw after intramedullary nail fixation of a pertrochanteric fracture. A 94-year-old Japanese female ...with a 5-year history of alendronate intake presented with prodromal pain in her right thigh after intramedullary nail fixation. Plain radiographs showed an incomplete noncomminuted transverse fracture at the distal screw, suggesting an atypical peri-implant femoral fracture. The pathogenesis of an atypical peri-implant femoral fracture could be a combined systemic bone metabolism disorder and repetitive overloading at the screw, similar to the pathogenesis of an atypical periprosthetic femoral fracture around stem implantation.
Purpose
The purpose of this review article was to investigate the incidence and predisposing factors for periprosthetic proximal femoral fractures (PFF) following total hip arthroplasty.
Methods
We ...performed a comprehensive search of the medical literature in MEDLINE and EMBASE databases to review articles related to PFF, their incidence and risk factors.
Results and Conclusions
The incidence of PPF after primary THA was, in general, lower than after revision THA both for intra- and postoperative PFF. The rate of intraoperative PFF ranged from 0.1 % to 27.8 % and of postoperative PFF from 0.07 % to 18 %. Predisposing factors for intraoperative PFF are osteoporosis, rheumatoid arthritis, femoral preparation and surgical technique used to insert the rasp or femoral component, the use of press-fit cementless stems, and revision THA. In case of postoperative PFF, the following seem to be significant risk factors: advanced age, female gender, post-traumatic osteoarthritis, osteoporosis and rheumatoid arthritis, proximal femoral deformities, previous surgery of the affected hip, implant type (especially cementless stems and press-fit implantation), technical errors such as cortical perforation, cortical stress risers, low-energy trauma, osteolysis, loosening and revision THA.
In the elderly, low-energy distal femur fractures (native or periprosthetic) can be devastating injuries, carrying high rates of morbidity and mortality, comparable with the hip fracture population. ...Poor, osteoporotic bone quality facilitates fracture in a vulnerable anatomical region, and as a result, operative fixation can be challenging. With goals of early mobilization to reduce subsequent complication risk, using the nail plate combination technique can offer stable, balanced fixation allowing for immediate weight bearing and early mobilization. We outline the rationale, technical steps, and early clinical outcomes after nail plate combination in the treatment of osteoporotic distal femur (native or periprosthetic) fractures.
Surgical treatment of periarticular and intra-articular fractures of the distal femur pose a significant challenge to the orthopedic surgeon. The primary goal of surgical treatment remains: ...restoration of the articular surface to the femoral shaft, while maintaining enough stability and alignment to enable early range of motion and rehabilitation. With appropriate surgical planning, these injuries can be managed with a variety of methods and techniques, while taking into account patients' functional goals, fracture characteristics, health comorbidities, bone quality, and risk of malunion and nonunion.
Distal femur fractures (DFFs) are common injuries with significant morbidity. Surgical options include open reduction and internal fixation (ORIF) with plates and/or intramedullary devices or a ...distal femur endoprosthesis (distal femur replacement DFR). A paucity of studies exist that compare the two modalities. The present study utilized a 1:2 propensity score match to compare 30-day outcomes of geriatric patients with DFFs who underwent an ORIF or DFR. The National Surgical Quality Improvement Program data from 2008 to 2019 were utilized to identify all patients who sustained a DFF and underwent either ORIF or DFR. This yielded 3,197 patients who underwent an ORIF versus 121 patients who underwent a DFR. A final sample of 363 patients (242 patients with ORIF vs. 121 with DFR) was obtained after a 1:2 propensity score match. Costs were obtained from the National Inpatient Sample database using multiple regression analysis and validated with a 7:3 train-test algorithm. Independent samples
-tests and chi-square analysis were conducted to assess cost and outcome differences, respectively. Patients who received a DFR had higher transfusion rates than ORIF (
= 0.021) and higher mean inpatient hospital costs (
= 0.001). Subgroup analysis for patients 80 years of age or older revealed higher 30-day unplanned readmission (0 vs. 18.2%;
< 0.001) and 30-day mortality (0 vs. 18.2%;
< 0.001) rates for patients undergoing ORIF compared with DFR. The total number of DFR cases needed to prevent one ORIF-related 30-day mortality for DFR for patients 80 years of age was 6 (95% confidence interval: 3.02-19.9). The mean hospital costs associated with preventing one case of death within 30 days from operation by undergoing DFR compared with ORIF was $176,021.39. Our results demonstrate higher rates of transfusion and increased inpatient costs among the DFR cohort compared with ORIF. However, we demonstrate lower rates of mortality for patients 80 years and older who underwent DFR versus ORIF. Future studies randomized controlled trials are necessary to validate the results of this study.
•Outside of a case report previously published by our institution, this is the first study to describe the use of a novel implant in the treatment of periprosthetic distal femur fractures.•We ...demonstrate that the use of a novel retrograde intramedullary nail with a 10° distal bend results in significantly better post-operative sagittal alignment than conventional nails with a 5° following treatment for periprosthetic distal femur fractures.•We demonstrate no difference in post-operative coronal alignment when comparing the novel retrograde intramedullary nail to conventional nails in the treatment of periprosthetic distal femur fractures.
Periprosthetic distal femur fractures (PPDFFs) are a common complication after total knee arthroplasty (TKA). In the setting of well-fixed TKA components, treatment options include retrograde intramedullary nailing (rIMN) or lateral locked plating. Treatment with rIMN has historically been associated with potential for extension deformity when using conventional nails. We hypothesized that the PPDFFs treated with an intramedullary nail with a specifically designed 10-degree distal bend for periprosthetic fractures would result in improved post-operative sagittal alignment compared to conventional intramedullary nails.
The study was conducted at a level-1 trauma center over a 12-year period (2010 - 2022). Patients over the age of 18 who sustained a PPDFF treated with rIMN were identified. The primary outcomes of the study were post-operative coronal and sagittal alignment determined by reviewing post-operative radiographs.
A total of 50 patients were included. Twenty-three patients were treated with a rIMN with a 10° distal bend. Twenty-seven patients were treated with a rIMN with distal bend of 5° The mean aPDFA for the 10° distal bend group was 81.7° compared to 92.8° in the 5° distal bend group (p<0.001). There were 3/23 (13%) significant sagittal plane deformities the 10° distal bend group compared to 11/27 (41%) in the 5° distal bend group (p = 0.03). There was one patient with a post-operative extension deformity in the 10° distal bend group compared to 11 patients in the 5° distal bend group (p = 0.02).
Retrograde intramedullary nailing of PPDFF with a 10° distal bend results in significantly better alignment in the sagittal plane when compared to a conventional 5° nail. The use of a 5° nail resulted in an extension deformity significantly more frequently. We therefore recommend the utilization of a rIMN with a 10° distal bend when treating PPDFFs.
Periprosthetic distal femur fractures are a common complication following total knee arthroplasty. While several studies report on the use of retrograde intramedullary nails in the treatment of periprosthetic distal femur fractures, there are limited reports of the use of a novel retrograde intramedullary nail with a 10° distal bend in the treatment of these injuries. Herein we present a radiographic study comparing coronal and sagittal postoperative alignment following treatment with retrograde intramedullary nails with a 10° distal bend versus conventional retrograde nails with a 5° distal bend.
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