Early Fracture Healing Research Articles

Histopathological and radiological evaluation of the efficacy of hydroxyapatite-boric acid and hydroxyapatite-magnesium coated Kirschner wires on fracture healing in femoral diaphyseal fractures: an experimental study.

Biomaterials used in fracture healing hold a significant place in orthopedics. This study aimed to develop biomaterials coated with hydroxyapatite (HA), boric acid (BA), and magnesium (Mg) and investigate their effects on fracture healing. Sixty female Wistar Albino rats were included in the study. The subjects were randomized into five groups. Cytotoxicity tests were performed on HA, BA, and Mg, and cell viability rates were calculated. Coatings were applied to Kirschner (K) wires at determined ratios. Group I was the control group with a steel K wire, Group II used HA-coated K wires, Group III used HA + BA-coated K wires, Group IV used HA + BA + Mg-coated K wires, and Group V used HA + Mg-coated K wires. A fracture was induced in the right femur of the subjects, followed by fixation with intramedullary K wires. The subjects were randomly divided into equal numbers and sacrificed at 6 and 12 weeks. Radiological and histopathological evaluations were performed. In direct cytotoxicity tests, the highest viability rate was observed in Group IV, while in indirect cytotoxicity tests, it was highest in Group II. In radiological evaluation at the 6th week, the highest scores were in Groups IV and V, while the lowest was in Group III. At the 12th week, the highest scores were in Groups II and V, while the lowest was in Group I. No significant differences were found between the groups (p = 0.837, p = 0.0479). In histopathological evaluation, a significant difference was observed between the groups (p < 0.001), with the highest scores in Group V. A correlation was found between the radiological and histopathological scores (p < 0.001, r = 0.438). It was found that HA + Mg significantly improved histological outcomes in fracture healing. Good histological results can be achieved with the use of Mg-containing implants in both early and late-stage fracture healing. Coating the biomaterials used in fracture fixation with Mg may lead to positive outcomes in fracture healing.

Short-term effectiveness of robot-guided femoral neck system combined with cannulated compression screw fixation in treatment of femoral neck fracture in young and middle-aged patients

To investigate short-term effectiveness of robot-guided femoral neck system (FNS) combined with cannulated compression screw (CCS) fixation in treatment of femoral neck fracture in young and middle-aged patients. A clinical data of 49 young and middle-aged patients with femoral neck fractures, who met the selection criteria and admitted between January 2021 and June 2023, was retrospectively analyzed. After reduction of femoral neck fractures, 27 cases were treated with robot-guided FNS fixation (FNS group) and 22 cases with robot-guided FNS and CCS fixation (FNS+CCS group). There was no significant difference in baseline data such as gender, age, cause of fracture, time from fracture to operation, fracture side, and classification (Garden classification and Pauwels classification) between the two groups ( P>0.05). The operation time, intraoperative blood loss, intraoperative fluoroscopy frequency, the time when the patient began bearing weight, and hip joint pain and functional scores (VAS score and Harris score) at last follow-up for two groups were recorded. Imaging re-examination was taken to evaluate the quality of fracture reduction, fracture healing, as well as the occurrence of fracture non-union, osteonecrosis of the femoral head, and femoral neck shortening. All operations were successfully completed and the incisions healed by first intention. There was no significant difference in operation time and intraoperative blood loss between the two groups ( P>0.05), and the intraoperative fluoroscopy frequency in FNS+CCS group significantly increased compared to FNS group ( P<0.05). All patients were followed up 12-18 months (mean, 14.1 months). Imaging re-examination showed that there was no significant difference in fracture reduction quality between the two groups ( P>0.05), but the fracture healing time was significantly shorter in FNS+CCS group than in FNS group, and weight-bearing began earlier ( P<0.05). The incidences of femoral neck shortening, fracture non-union, and osteonecrosis of the femoral head were lower in FNS+CCS group than in FNS group, and there was significant difference in the incidence of femoral neck shortening between groups ( P<0.05). At last follow-up, there was no significant difference in VAS scores between the two groups ( P>0.05). However, the Harris score was significantly higher in FNS+CCS group than in FNS group ( P<0.05). Compared with FNS fixation alone, robot-guided FNS combined with CCS fixation in the treatment of femoral neck fractures in young and middle-aged patients has obvious advantages in terms of early weight bearing and fracture healing, improves fracture healing rate, effectively prevents postoperative complications, and can obtain good short-term effectiveness.

Clinical outcomes of retrograde intramedullary multiple pinning for proximal humeral fractures using a modified palm tree technique

BackgroundRetrograde intramedullary multiple pinning using a modified palm tree technique for proximal humeral fractures has attracted interest from surgeons because of its minimal invasiveness into the soft tissue around the shoulder joints. We aimed to evaluate the clinical and radiological outcomes of this procedure. MethodsThis retrospective study included 21 patients who underwent surgery using a modified palm tree technique for proximal humeral fractures between March 2010 and March 2022. Patients with two- and three-part proximal humeral fractures that could be reduced by closed manipulation under general anesthesia were included in this study. All patients were clinically evaluated using the Japanese Orthopaedic Association (JOA) and University of California at Los Angeles (UCLA) shoulder scores. Postoperative radiographic findings, including fracture healing and signs of pinning-related complications, were evaluated. ResultsTwenty-one shoulders in 21 patients (9 men and 12 women) with mean age at surgery of 66.3 ± 19.3 years were evaluated. The mean period until bone union was 2.6 ± 0.7 months. The mean JOA and UCLA shoulder scores at the final follow-up were 84.8 ± 12.1 and 27.5 ± 5.4, respectively. Perforation of the humeral head by Kirschner (K) wires was observed in 9 of the 21 (42.9 %) shoulders. The JOA and UCLA shoulder scores at the final follow-up were not significantly different between the groups with and without perforations (p = 0.41 and 0.27, respectively). The oblique or Y-view detected significantly more wires with perforation of the humeral head than did the anteroposterior view (6 vs. 15 wires, p < 0.01). ConclusionsThe modified palm tree technique for proximal humeral fractures demonstrated good postoperative clinical outcomes and early fracture healing. However, modifications in postoperative management and surgical techniques should be considered to reduce the high rate of perforation of the humeral head by K-wires.

Prospective study on functional outcome of distal femur fracture treated by open reduction and internal fixation using distal femur locking plate in Tibebe Ghion Specialized Hospital, Bahirdar, North West Ethiopia

BackgroundDistal femur fractures account for 6% of femur fractures. The treatment of distal femur fractures is challenging. Historically, nonoperative management has been the mainstay of management, which has evolved to operative management. There is no single implant used for all types of distal femur fractures. The implant evolves with time. The introduction of a distal femur locking plate (DF LCP) has had a great impact on the treatment. In developing countries like Ethiopia, there is scarcity of studies on functional outcome of operative treatment. So, this study aimed to assess the functional outcome of distal femur fractures treatment using distal femur locking plate.MethodsThis prospective cohort study was carried out among adult patients with distal femur fractures treated using distal femur locking plate at Tibebe Ghion Specialized Hospital from august 2022 to July 2023. A total of 60 patients with AO Type A and Type C fracture were included. All patients were followed for 6 months. Functional outcomes were assessed using Neer’s scoring system. Data was entered and analyzed using SPSS 27. Frequency, mean and cross tabulation were used to summarize descriptive statistics. Multinomial logistic regression was used to test the associations.ResultsIn our study out of 60 patients ,48.3% (29) had excellent functional outcomes, 30% (18) had good functional outcomes, 10% (6) had fair functional outcomes and 11.7% (7) had unsatisfactory functional outcomes according to Neer’s scoring system. Patients with closed distal femur fractures had 5 times higher probability of excellent functional outcome than those patients with open distal femur fractures (AOR (2.49(5.8 ,1.07)). Patients who had regular follow up had 7 times higher probability of excellent functional outcome than those who had no regular follow up (AOR 7.16(1.11,46.22)). The average union period was 4.63 months, with only 2 patients experiencing delayed union.ConclusionClosed fracture and regular follow up were determining factors for better functional outcomes. Closed fractures preserve the biological environment, which facilitates early fracture healing. The regular follow up helped patients to assess their rehabilitation status and pick any complication early.

Identification of the miRNA-mRNA regulatory network in a mouse model of early fracture.

Fracture healing is a complex process that involves multiple molecular events, and the regulation mechanism is not fully understood. We acquired miRNA and mRNA transcriptomes of mouse fractures from the Gene Expression Omnibus database (GSE76197 and GSE192542) and integrated the miRNAs and genes that were differentially expressed in the control and fracture groups to construct regulatory networks. There were 130 differentially expressed miRNAs and 4,819 differentially expressed genes, including 72 upregulated and 58 downregulated miRNAs, along with 2,855 upregulated and 1964 downregulated genes during early fracture healing. Gene ontology analysis revealed that most of the differentially expressed genes were enriched in the extracellular matrix (ECM) structure and the ECM organization. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment suggested cell cycle, DNA replication, and mismatch repair were involved in the progression of fracture healing. Furthermore, we constructed a molecular network of miRNAs and mRNAs with inverse expression patterns to elucidate the molecular basis of miRNA-mRNA regulation in fractures. The regulatory network highlighted the potential targets, which may help to provide a mechanistic basis for therapies to improve fracture patient outcomes.

Endothelial to mesenchymal Notch signaling regulates skeletal repair.

We present a transcriptomic analysis that provides a better understanding of regulatory mechanisms within the healthy and injured periosteum. The focus of this work is on characterizing early events controlling bone healing during formation of periosteal callus on day 3 after fracture. Building on our previous findings showing that induced Notch1 signaling in osteoprogenitors leads to better healing, we compared samples in which the Notch 1 intracellular domain is overexpressed by periosteal stem/progenitor cells, with control intact and fractured periosteum. Molecular mechanisms and changes in skeletal stem/progenitor cells (SSPCs) and other cell populations within the callus, including hematopoietic lineages, were determined. Notably, Notch ligands were differentially expressed in endothelial and mesenchymal populations, with Dll4 restricted to endothelial cells, whereas Jag1 was expressed by mesenchymal populations. Targeted deletion of Dll4 in endothelial cells using Cdh5CreER resulted in negative effects on early fracture healing, while deletion in SSPCs using α-smooth muscle actin-CreER did not impact bone healing. Translating these observations into a clinically relevant model of bone healing revealed the beneficial effects of delivering Notch ligands alongside the osteogenic inducer, BMP2. These findings provide insights into the regulatory mechanisms within the healthy and injured periosteum, paving the way for novel translational approaches to bone healing.

Fracture haematoma proteomics.

The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies. A porcine multiple trauma model was used in which two fracture treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). fxH was harvested and analyzed using liquid chromatography-tandem mass spectrometry. Per group, discriminating proteins were identified and protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase. The early fxH proteome was characterized by immunomodulatory and osteogenic proteins, and proteins involved in the coagulation cascade. Treatment-specific proteome alterations were observed. The fxH proteome of the ETC group showed increased expression of pro-inflammatory proteins related to, among others, activation of the complement system, neutrophil functioning, and macrophage activation, while showing decreased expression of proteins related to osteogenesis and tissue remodelling. Conversely, the fxH proteome of the DCO group contained various upregulated or exclusively detected proteins related to tissue regeneration and remodelling, and proteins related to anti-inflammatory and osteogenic processes. The early fxH proteome of the ETC group was characterized by the expression of immunomodulatory, mainly pro-inflammatory, proteins, whereas the early fxH proteome of the DCO group was more regenerative and osteogenic in nature. These findings match clinical observations, in which enhanced surgical trauma after multiple trauma causes dysbalanced inflammation, potentially leading to reduced tissue regeneration, and gained insights into regulatory mechanisms of fracture healing after severe trauma.

Intercalary Resection of the Tibia for Primary Bone Tumors: Are Vascularized Fibula Autografts With or Without Allografts a Durable Reconstruction?

Intercalary Resection of the Tibia for Primary Bone Tumors: Are Vascularized Fibula Autografts With or Without Allografts a Durable Reconstruction?

The impact of osteoporosis and diabetes on fracture healing under different loading conditions

BackgroundOsteoporosis and diabetes are two prevalent conditions among the elderly population. Each of these conditions can profoundly influence the fracture healing process by disturbing the associated inflammatory process. However, the combined effects of osteoporosis and diabetes on fracture healing remain unclear. Therefore, the purpose of the present study is to investigate the role of osteoporosis and diabetes in fracture healing and the underlying mechanisms by developing numerical models. MethodThis study introduces a numerical model that consists of a three-dimensional model of a tibia fracture stabilized by a Locking Compression Plate (LCP), coupled with a two-dimensional axisymmetric model which illustrates the transport and reactions of cells and cytokines throughout the inflammatory phase in early fracture healing. First, the model parameters were calibrated using available experimental data. The model was then implemented to predict the healing outcomes of fractures under five varied conditions, consisting of both osteoporotic and non-osteoporotic bones, each subjected to different physiological loads. ResultsThe instability of the fracture callus can significantly escalate in osteoporotic fractures (e.g., when a 150 N physiological load is applied, the unstable region of the osteoporotic fracture callus can reach 26 %, in contrast to 12 % in non-osteoporotic fractures). Additionally, the mesenchymal stem cells (MSCs) proliferation and differentiation can be disrupted in osteoporotic fracture compared to non-osteoporotic fractures (e.g., on the 10th day post-fracture, the decrease in the concentration of MSCs, osteoblasts, and chondrocytes in osteoporotic fractures is nearly double that in non-osteoporotic fractures under a 150 N). Finally, the healing process of fractures can suffer significant impairment when osteoporosis coexists with diabetes (e.g., the concentration of MSCs can be drastically reduced by nearly 37 % in osteoporotic fractures under diabetic conditions when subjected to a load of 200 N) ConclusionsFracture calluses destabilized by osteoporosis can negatively affect the fracture healing process by disrupting the proliferation and differentiation of mesenchymal stem cells (MSCs). Moreover, when osteoporosis coexists with diabetes, the fracture healing process can severely impair the fracture healing outcomes.

Key Trace Elements Zinc and Magnesium Levels Decline After Fracture in a Rat Model

Category: Basic Sciences/Biologics; Basic Sciences/Biologics Introduction/Purpose: Zinc and magnesium are crucial for bone health, and their deficiencies can lead to impaired bone metabolism and repair. Although enhancing their bioavailability has been linked to better fracture healing, their levels during healing have not been studied. We hypothesized that zinc and magnesium levels transiently decrease at the fracture site compared to intact bone. This study is the first to explore temporal trace element levels during the initial stages of fracture healing. The findings will reveal when each element changes its concentration at the fracture site, which is associated with specific functions necessary for appropriate healing. Understanding the connection between trace element concentration and repair processes could lead to more effective treatment or supplementation during fracture healing. Methods: Following induction of a femur fracture in male BB Wistar rats, injured and intact contralateral femurs were harvested at 1- (n=3), 3- (n=4), and 7-days (n=3) after fracture. Fracture segments 10mm in length were resected 5mm from the center of the callus in either direction. Contralateral non-fractured femur segments were resected from the same region within the femoral diaphysis. Samples were analyzed via inductively coupled mass spectrometry using an Agilent ICP-MS 7900 (Agilent Technologies, Santa Clara, CA). Data was converted from ppb to percent weight zinc and magnesium per weight of bone (w/w%). The difference between zinc and magnesium in contralateral intact bone vs. fractured bone was calculated and averaged (∆) for each group. The average % change were also determined. An independent sample two-tailed t-test was performed comparing average w/w% of zinc and magnesium between fracture and contralateral samples. A p-value of &lt; 0.05 was considered significant. Results: After 1-day post-fracture, there was a -29.09 average % change in zinc levels (∆ 6.90x10^-03 ± 5.05x10^-03) (p = 0.033) and a -25.76 average % change in magnesium levels (∆ 1.21x10^-01 ± 7.36x10^-02 w/w%) (p = 0.241) between fractured and non- fractured femurs. After 3-days post-fracture, there was a -22.51 average % change in zinc levels (∆ 5.45x10^-03 ± 3.95x10^-03 w/w%) (p = 0.022) and a -33.07 average % change in magnesium levels (∆ 1.84x10^-01 ± 1.05x10^-01 w/w%) (p = 0.025). After 7- days post-fracture, there was a -9.40 average % change in zinc levels (∆ 1.90x10^-03 ± 3.98x10^-03) (p = 0.377) and a -17.88 average % change in magnesium levels (∆ 9.04x10^-02 ± 1.24x10^-01 w/w%) (p = 0.159) between fractured and non-fractured femurs. Conclusion: Previous research has established the significance of trace elements, namely zinc and magnesium, in the process of fracture healing. Zinc has been shown to improve fracture healing, while magnesium has been found to play a role regulating inflammation during early fracture healing. The findings of this study corroborate our hypothesis that levels of these elements transiently decline following fracture. By evaluating these changes in trace element levels, we can gain a better understanding of their function in the fracture healing process. These observations may offer insight into potential therapeutic approaches utilizing zinc and magnesium for fracture healing in the future.

Fixation of Tibial Shaft Fracture by Interlocking Nail without Proximal Screws

Tibia is the most commonly fractured long bone. In adults it takes 4 to 6 months to heal depending on the severity ofinjury and method of treatment. Rate of complications are also high. Locked intramedullary nailing is the preferredtreatment for tibial shaft fractures. When locked proximally and distally, removal of one set of screws, especially intransverse and short oblique fractures are required for dynamization before weight bearing. Fail to do this timely,many of these patients present with nonunion and implant failure. The purpose of the study was to enhance healing oftibial shaft fracture by early weight bearing, at the same time minimizing the complications and early return to work.Stable open type- I, II &amp; closed tibial shaft fractures from the isthmus to 4 cm above the distal articular surface of thetibia were fixed by locking nail without proximal screws. This prospective study was done from June 2009 to July2014 on 410 patients treated at several hospitals of Faridpur city. All the operations were done in closed methodwithout any C-Arm monitoring. Patients were allowed to move with crutch and controlled partial weight bearingwithin two to four weeks of operation. All patients were followed up for five years. In most cases the nail wereremoved in one to two years. Early weight bearing causes compression and intermittent micro movements at thefracture site. The fractures heal as early as in eight to twelve weeks and no nonunion or implant failure wereencountered. Knee pain was complained by 41 patients (10%), disappeared after removal of the nail. Superficialinfection developed in 8 cases (1.95%), controlled in 2 to 3 weeks and deep infections were encountered in 8 cases(1.95%) with delaying union but eradicated spontaneously as the fracture healed. Deep infection occurs only in openfractures. Although five years period is not enough to comment about development of secondary osteoarthritis, weencountered no such cases till now. So, closed reduction and internal fixation (CRIF) of stable open type-I, II &amp;closed tibial shaft fractures from the isthmus to 4 cm above the distal articular surface of the tibia by interlockingnailing with distal locking screws only, allows early controlled weight bearing, thereby early fracture healing and lesschance of implant failure.&#x0D; Bangabandhu Sheikh Mujib Med. Coll. J. 2022;1(1):33-36

Influence of knee flexion on early femoral fracture healing: A combined analysis of musculoskeletal dynamics and finite elements

Background and ObjectivesKnee flexion causes a certain amount of misalignment and relative movement of the fractured ends of the femur fracture, and if the flexion angle is too large it will affect the stability of the fracture and the healing process, making it challenging to design a safe range of flexion. However, due to a lack of basic understanding of the effect of knee flexion on the mechanical environment at the fracture site, clinicians are often unable to provide an objective and safe range of motion in flexion based on subjective experience. The aim of this study was to evaluate the effect of knee flexion on plate and fracture healing using finite element analysis (FEA). MethodsA human musculoskeletal model was constructed based on CT scan data, and the mechanical properties of the fracture site were changed by adjusting the knee flexion angle. The joint forces, muscle forces and moments acting on the femur were obtained by inverse dynamics analysis, and the biomechanical properties of the fracture-plate system were analyzed using finite elements. A finite element model of the fracture-plate system without muscle loading was also constructed. The effect of knee flexion on the safety of plate fixation and fracture healing was evaluated in terms of the biomechanical properties of the plate and the interfragmentary motion of the fracture. ResultsAs the knee flexion angle increases, the von Mises stress of the locked compression plate (LCP) first increases, then decreases, then increases again. The deformation from compression bending to tension twisting occurs simultaneously. At 30° of flexion, shear interfragmentary motion (SIM) was dominant and inhibited fracture healing; at more than 45° of flexion, the plate was twisted and deformed to the lateral side of the body, and the fracture site underwent greater misalignment and relative motion, with destructive effects on bone scabs and healing tissues. If muscle loading is not taken into account, the plate will undergo predominantly bending deformation and will overestimate the interfragmentary strain in the far and near cortex. ConclusionsKnee flexion causes the plate to deform from compression bending to extension and torsion, which has an important impact on the safety and healing process of the fracture, and this study provides a biomechanical basis to guide the clinician in the post-operative rehabilitation of femoral fractures in the clinical setting.

Herbal Extracts of Ginseng and Maqui Berry Show Only Minimal Effects on an In Vitro Model of Early Fracture Repair of Smokers.

Smoking is a major risk factor for delayed fracture healing, affecting several aspects of early fracture repair, including inflammation, osteogenesis, and angiogenesis. Panax ginseng (GE) and maqui berry extract (MBE) were shown in our previous studies to reduce smoke-induced cellular damage in late bone-healing in vitro models. We aimed here to analyze their effects on the early fracture repair of smokers in a 3D co-culture model of fracture hematomas and endothelial cells. Both extracts did not alter the cellular viability at concentrations of up to 100 µg/mL. In early fracture repair in vitro, they were unable to reduce smoking-induced inflammation and induce osteo- or chondrogenicity. Regarding angiogenesis, smoking-induced stress in HUVECs could not be counteracted by both extracts. Furthermore, smoking-impaired tube formation was not restored by GE but was harmed by MBE. However, GE promoted angiogenesis initiation under smoking conditions via the Angpt/Tie2 axis. To summarize, cigarette smoking strikingly affected early fracture healing processes in vitro, but herbal extracts at the applied doses had only a limited effect. Since both extracts were shown before to be very effective in later stages of fracture healing, our data suggest that their early use immediately after fracture does not appear to negatively impact later beneficial effects.

EFFECT OF BISPHOSPHONATES ON FRACTURE HEALING AMONG THE ELDERLY PEOPLE WITH INTERTROCHANTERIC FRACTURE

Background: Hip fractures in the elderly are commonly associated with osteoporosis, and the surgical outcome is therefore inuenced by its concurrent management. Understanding the role of the osteoporosis drug and its healing mechanism with the fracture is crucial for managing the fracture and osteoporosis properly. The purpose of our study is to determine whether bisphosphonate administration in stable intertrochanteric (IT) fractures helps in early fracture healing. Aim: The aim of the study is to assess the effect of bisphosphonates on intertrochanteric fracture among elderly people aged &gt;50 years in preoperatively conrmed osteoporotic patients. Methodology: This is a non-randomized study done in the Department of Orthopaedics at Assam Medical College, Dibrugarh for a period of 1 year, from May 2021 to April 2022. The total sample size attained was 50, consisting of 25 patients in each group. Demographic details like age, sex, mean bone mineral density of hip and spine, and mean body mass index were obtained. The collected data was entered into MS Excel and statistics were done with SPSS 16. Results: Among the study participants, the majority were female: 15(60%) in the bisphosphonate group and 19(76%) in the control group; the rest were males. The mean age of the study participants was 56±2.1 years. In both groups, xation of the fracture was done by intramedullary nailing. The mean time difference in fracture healing between the two groups was not found to be signicant. Conclusion:The mean healing time for the fracture healing was not found to be statistically signicant when compared with the placebo group

An experimental study on the effects of splenectomy on bone fracture healing

Bone fracture healing is a complex process involving multiple mechanisms where immune system has vital role. The spleen is a part of this process and its effect on bone metabolism is not completely understood. Herein, the effects of simultaneous bone fractures and splenectomy were evaluated regarding early and late periods of fracture healing in rats. The closed fracture model was applied in sixty-four healthy male Wistar-albino rats. Rats were randomly selected and divided into four groups. The splenectomy was carried out in two groups. The early period was declared as three weeks and late period as five weeks for evaluating the fracture healing in rats,(Groups A: splenectomized 3rd week, Groups B: non-splenectomized 3rd week, Groups C: splenectomized 5th week, and Groups D: non-splenectomized 5th week). The groups were compared regarding radiological, biomechanical, and histopathological aspects at 3rd and 5th weeks of fracture healing. The callus/bone volume ratios of Groups C and D were lower than those of Groups A and B (A–C, p ≤ 0.001; B–D, p ≤ 0.001). Radiographic Union Score for Tibial Fracture scores of Groups C and D were higher than those for Groups A and B (A–C, p ≤ 0.001; B–D, p ≤ 0.001). Bone mineral density measurements of Groups C and D were higher than those for Groups A and B (A–C, p ≤ 0.001; A–D, p ≤ 0.001; B–C, p ≤ 0.001 and B–D, p ≤ 0.001). The histological scoring of Groups A was lower than Groups C and D (A–C, p = 0.004; A–D, p = 0.001). Splenectomy may thus adversely affect the early phase fracture healing.

Comparative study of range of motion and anterior knee pain in parapatellar versus trans patellar approach in tibia nailing

&lt;p&gt;&lt;strong&gt;Background:&lt;/strong&gt; Tibial shaft fractures are common traumatic fractures especially in road traffic accidents. Intramedullary interlocking nailing is considered treatment of choice tibial diaphyseal fractures, minimizing soft tissue injury and permitting early weight bearing and fracture healing. Anterior knee pain and reduced range of motion are some common complications that patients have to face in post-operative period.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The&lt;strong&gt; &lt;/strong&gt;60 patients of both sex with traumatic diaphyseal tibial shaft fractures were included in this study out of which 30 were operated with interlocking tibia nailing with trans patellar (tendon splitting) approach while 30 were operated with medial parapatellar approach for tibia nail insertion. Range of motion at knee joint (in degrees) and anterior knee pain (on visual analogue scale) was evaluated on post-operative day 1, 2 weeks, 1 month, 3-month post operatively and compared for both groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Mean anterior knee pain was significantly lower in parapatellar approach group at 2 weeks, 1 month and 3 months while there was no significant difference on post-operative day 1. Mean range of motion at knee joint was more in parapatellar approach group on post-operative day 1 and 2 weeks while there was no significant difference in range of motion after 2 weeks.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In our study medial parapatellar approach is superior than tendon splitting approach with comparatively greater range of motion and lesser anterior knee pain. Thus, medial parapatellar approach should be encouraged for interlocking tibia nailing.&lt;/p&gt;

The effects of mechanical instability on PDGF mediated inflammatory response at early stage of fracture healing under diabetic condition

Background and ObjectiveMechanical stability plays an important role in fracture healing process. Excessive interfragmentary movement will continuously damage the tissue and newly formed capillaries at the fracture site, which leads to overproduction of platelet-derived growth factor (PDGF) that attracts more macrophages into fracture callus, ultimately persistent and enhanced inflammatory response happens. For diabetic condition, the impact of mechanical instability of fracture site on inflammatory response could be further compliciated and the relevant research in this field is relatively limited. MethodsBuilding on previous experimental studies, this study presents a numerical model consisting of a system of reactive-transport equations representing the transport as well as interactions of different cells and cytokines within the fracture callus. The model is initially validated by available experimental data, and then implemented to investigate the role of mechanical stability of fracture site in inflammatory response during early stage of healing. It is assumed that there is an increased release of PDGF due to the rupture of blood vessels resulting from mechanical instability, which leads to increased production of inflammatory cytokines (i.e., TNF-α). The bone healing process under three different conditions were investigated, i.e., mechanically stable condition with normal inflammatory response (Control, Case 1), mechanically unstable condition with normal inflammatory response (Case 2) and mechanically unstable condition with diabetes (Case 3). ResultsMechanical instability can promote the macrophage infiltration and thus induce an enhanced and prolonged inflammatory response, which could impede the MSCs proliferation during the early fracture healing stage (e.g., compared with the control condition, the MSCs concentration in unstable fracture with normal inflammatory response can be reduced by 3.2% and 5.2% on day 2 and day 10 post-fracture, respectively). Under diabetic condition, the mechanical instability of fracture site could lead to a significant increase of TNF-α concentration in fracture callus (Case 3) in comparison to control (Case 1) (e.g., three-fold increase in TNF-α concentration compared to control). In addition, the results show that the mechanical instability affects the cell differentiation and proliferation in fracture callus in a spatially dependent manner, e.g., for diabetic fracture patients, the mechanical instability could potentially decrease the concentration of MSCs, osteoblasts and chondrocytes by around 39%, 30% and 29% in cortical callus, respectively, in comparison to control. ConclusionThe mechanical instability together with diabetic condition can significantly affect the natural resolution of inflammation during early stage of healing by turning acute inflammation into chronic inflammation which is characterized by a continuously upregulated TNF-α pathway.

A comparison of functional and radiological outcome of combine compression antegrade intertrochanteric nail (InterTan) and proximal femoral nail anti-rotation II (PFNA-II) in elderly patients with intertrochanteric fractures.

To compare the functional and radiological outcome of combine compression interlocking intramedullary nail (InterTan) and proximal femoral nail anti-rotation II (PFNA-II) in the treatment of elderly patients with intertrochanteric fractures. As a retrospective cohort study, records of 88 patients with intertrochanteric fractures treated in our hospital from January 1st, 2019 to July 31st, 2021 were retrospectively reviewed. According to treatment records, it included 45 patients treated with InterTan (Group-A) and 43 patients treated with PFNA-II (Group-B). The operation safety and functional rehabilitation of the two groups were compared and analyzed. This study included 88 patients with intertrochanteric fractures (mean [SD] age, 68.72 [0.10] years at baseline), of whom 52 (59.09%) were males and 36 (40.91%) were females. Operation time and intraoperative blood loss in Group-B were less than Group-A, while fracture healing time was shorter in Group-A. The fracture separation distance was measured four weeks after the operation. The widening rate of the fracture line in Group-A was lower than Group-B (4.4% vs.18.6%; P<0.05). The incidence of complications in Group-A was lower than Group-B (4.4% vs.18.6%; P<0.05). At three, six and twelve months after the operation, the Harris hip score of the two groups was higher than at discharge (P<0.05), with no significant difference between groups (P>0.05). We found no significant difference in the functional outcome in elderly patients with intertrochanteric fractures treated with InterTan and PFNA-II. Early fracture healing and reduced complication rate however has been noted with InterTan.

Signature of circulating small non-coding RNAs during early fracture healing in mice

Fracture healing is a complex process with multiple overlapping metabolic and differentiation phases. Small non-coding RNAs are involved in the regulation of fracture healing and their presence in circulation is under current interest due to their obvious value as potential biomarkers. Circulating microRNAs (miRNAs) have been characterized to some extent but the current knowledge on tRNA-derived small RNA fragments (tsRNAs) is relatively scarce, especially in circulation.In this study, the spectrum of circulating miRNAs and tsRNAs was analysed by next generation sequencing to show their differential expression during fracture healing in vivo. Analysed tsRNA fragments included stress-induced translation interfering tRNA fragments (tiRNAs or tRNA halves) and internal tRNA fragments (i-tRF), within the size range of 28–36 bp. To unveil the expression of these non-coding RNAs, genome-wide analysis was performed on two months old C57BL/6 mice on days 1, 5, 7, 10, and 14 (D1, D5, D7, D10, and D14) after a closed tibial fracture.Valine isoacceptor tRNA-derived Val-AAC 5′end and Val-CAC 5′end fragments were the major types of 5′end tiRNAs in circulation, comprising about 65 % of the total counts. Their expression was not affected by fracture. After a fracture, the levels of two 5′end tiRNAs Lys-TTT 5′ and Lys-CTT 5′ were decreased and His-GTG 5′ was increased through D1-D14. The level of miR-451a was decreased on the first post-fracture day (D1), whereas miR-328-3p, miR-133a-3p, miR-375-3p, miR-423-5p, and miR-150-5p were increased post-fracture. These data provide evidence on how fracture healing could provoke systemic metabolic effects and further pinpoint the potential of small non-coding RNAs as biomarkers for tissue regeneration.

Smoking Impairs Hematoma Formation and Dysregulates Angiogenesis as the First Steps of Fracture Healing.

Bone fracture healing is an overly complex process in which inflammation, osteogenesis, and angiogenesis are tightly coupled, and delayed fracture repair is a very common health risk. One of the major causes of delayed healing is the formation of insufficient vasculature. Precise regulation of blood vessels in bone and their interplay with especially osteogenic processes has become an emerging topic within the last years; nevertheless, regulation of angiogenesis in (early) diseased fracture repair is still widely unknown. Here, we aim to develop an in vitro model for the analysis of early fracture healing which also enables the analysis of angiogenesis as a main influencing factor. As smoking is one of the main risk factors for bone fractures and developing a delay in healing, we model smoking and non-smoking conditions in vitro to analyze diverging reactions. Human in vitro fracture hematomas mimicking smokers’ and non-smokers’ hematomas were produced and analyzed regarding cell viability, inflammation, osteogenic and chondrogenic differentiation, and angiogenic potential. We could show that smokers’ blood hematomas were viable and comparable to non-smokers. Smokers’ hematomas showed an increase in inflammation and a decrease in osteogenic and chondrogenic differentiation potential. When analyzing angiogenesis, we could show that the smokers’ hematomas secrete factors that drastically reduced HUVEC proliferation and tube formation. With an angiogenesis array and gene expression analysis, we could identify the main influencing factors: Anpgt1/2, Tie2, and VEGFR2/3. In conclusion, our model is suitable to mimic smoking conditions in vitro showing that smoking negatively impacts early vascularization of newly formed tissue.