Aims

The aim of this study was to investigate the safety and efficacy of 3D-printed modular prostheses in patients who underwent joint-sparing limb salvage surgery (JSLSS) for malignant femoral diaphyseal bone tumours.

At-home softcast removal with no routine clinical follow-up has shown to be safe and effective following paediatric orthopaedic trauma. It minimises clinician contact time and reduces cost. However, there is limited data on the caregiver experience.

Retrospective analysis of paediatric fractures requiring application of circumferential softcast that was later removed at home. Two time points were included: (1)July–September 2022, (2)February–April 2023. Demographics data included age, fracture classification, angulation, manipulation requirement, complications or unplanned re-attendance. Caregivers were given an information leaflet on cast removal. Caregivers completed a telephone Likert questionnaire reviewing time taken to remove cast, qualitative descriptors of cast removal and overall satisfaction.

77 families were contacted at mean 93 days post injury. Mean age was 7.5 years. 41(53%) were distal radius and 20(26%) both-bone forearm fractures. The remaining were hand, elbow or tibia injuries. 40(52%) injuries required manipulation under procedural sedation with mean sagittal angulation 24 degrees. 13(17%) patients re-attended with cast problems. Caregivers estimated a mean 13 minutes to remove cast. 83% found it ‘extremely’ or ‘somewhat’ easy. 75% were ‘extremely’ or ‘somewhat’ satisfied. 71% were ‘extremely’ or ‘somewhat’ likely to recommend at-home cast removal. Qualitative descriptors ranged from from ‘traumatising’ to ‘fun’ and ‘straightforward’.

The experience at our tertiary centre confirms at-home softcast removal with no further orthopaedic follow-up is safe and feasible, even in those requiring manipulation under sedation. The majority of families reported a positive experience; this however is not universal. Adequate patient information resources are integral to a positive caregiver's experiences.

In relation to regenerative therapies in osteoarthritis and cartilage repair, mesenchymal stromal cells (MSCs) have immunomodulatory functions and influence macrophage behaviour. Macrophages exist as a spectrum of pro-(M1) and anti-(M2) inflammatory phenotypic subsets. In the context of cartilage repair, we investigated MSC-macrophage crosstalk, including specifically the priming of cartilage cells by macrophages to achieve a regenerative rather than fibrotic outcome. Human monocytes were isolated from blood cones and differentiated towards M1 and M2 macrophages. Monocytes (Mo), M1 and M2 macrophages were cultured directly and indirectly (trans-well system) with human bone marrow derived MSCs. MSCs were added during M1 polarisation and separately to already induced M1 cells. Outcomes (M1/M2 markers and ligands/receptors) were evaluated using RT-qPCR and flow cytometry. Influence on chondrogenesis was assessed by applying M1 and M2 macrophage conditioned media (CM) sequentially to cartilage derived cells (recapitulating an acute injury environment). RT-qPCR was used to evaluate chondrogenic/fibrogenic gene transcription. The ratio of M2 markers (CD206 or CD163) to M1 markers (CD38) increased when MSCs were added to Mo/M1 macrophages, regardless of culture system used (direct or indirect). Pro-inflammatory markers (including TNFβ) decreased. CXCR2 expression by both M1 macrophages and MSCs decreased when MSCs were added to differentiated M1 macrophages in transwell. When adding initially M1 CM (for 12 hours) followed by M2 CM (for 12 hours) sequentially to chondrocytes, there was a significant increase of Aggrecan and Collagen type 2 gene expression and decrease in fibroblastic cell surface markers (PDPN/CD90). Mo/M1 macrophages cultured with MSCs, directly or indirectly, are shifted towards a more M2 phenotype. Indirect culture suggests this effect can occur via soluble signaling mediators. Sequential exposure of M1CM followed by M2CM to chondrocytes resulted in increased chondrogenic and reduced fibrotic gene expression, suggesting that an acute pro-inflammatory stimulus may prime chondrocytes before repair.

Cell culture on tissue culture plastic (TCP) is widely used across biomedical research to understand the in vivo environment of a targeted biological system. However, growing evidence indicates that the characteristics of cells investigated in this way differ substantially from their characteristics in the human body. The limitations of TCP monolayer cell cultures are especially relevant for chondrocytes, the cell population responsible for producing cartilage matrix, because their zonal organization in hyaline cartilage is not preserved in a flattened monolayer assay. Here, we contrast the response of primary human chondrocytes to inflammatory cytokines, tumor necrosis factor-alpha and interferon-gamma, via transcriptional, translational, and histological profiling, when grown either on TCP or within a 3D cell pellet (scaffold-less). We focus on anti-apoptotic (Bcl2), pro-apoptotic (Bax, Mff, Fis1), and senescent (MMP13, MMP1, PCNA, p16, p21) markers. We find that the 3D environment of the chondrocyte has a profound effect on the behavior and fate of the cell; in TCP monolayer cultures, chondrocytes become anti-apoptotic and undergo senescence in response to inflammatory cytokines, whereas in 3D cell pellet cultures, they exhibit a pro-apoptotic response. Our findings demonstrate that chondrocyte culture environment plays a pivotal role in cell behavior, which has important implications for the clinical applicability of in vitro research of cartilage repair. Although there are practical advantages to 2D cell cultures, our data suggest researchers should be cautious when drawing conclusions if they intend to extrapolate findings to in vivo phenomena. Our data demonstrates opposing chondrocyte responses in relation to apoptosis and senescence, which appear to be solely reliant on the environment of the culture system. This biological observation highlights that proper experimental design is crucial to increase the clinical utility of cartilage repair experiments and streamline their translation to therapy development.

Aims

Knee osteoarthritis (OA) involves a variety of tissues in the joint. Gene expression profiles in different tissues are of great importance in order to understand OA.

Mental disorders in particular depression and anxiety have been reported to be prevalent among patients with spinal pathologies. Goal of the current study was to analyze the relationship of Zung pre- and post-op score to other PROs and length of stay. Secondary outcomes included revision surgery and post-operative infections.

Data from the international multicenter prospective spine degenerative surgery data repository, DegenPRO v1.1 (AO Spine Knowledge Forum Degenerative) were utilized. Patients undergoing cervical or lumbar procedure were included. Patient's demographics, Charlson Comorbidity Index, surgical information, Zung score, NDI, pain related PROs and EQ-5D, and complications at surgery and at various post-op time periods. Except for hospital duration, data were analyzed, using multivariable mixed linear models. A robust linear regression model was used to assess the association between Zung score and hospital duration. All models were adjusted for gender and age.

42 patients had Zung score administered. Among those patients 22 (52%) were within normal range, 18 (43%) were mildly and 2 (5%) severely depressed. 62% of the patients had a lumbar pathology with fusion procedures being the most common. Median EQ-5D (3L) score at surgery was significantly higher (0.7, IQR: 0.4-0.7) for patients within normal range than for those with mild (0.4, IGR: 0.3-0.7) or severe depression (0.3, IQR: 0.3-0.3, p-value: 0.05). Compared to patients within normal Zung range, mixed models, indicated lower EQ-5D (3L) score values and higher values for neck and arm pain at surgery with both PROs and EQ-5D (3L) improving in patients with depression over the follow-up time. No association was found between Zung score and hospital length of stay.

The initial analysis showed that 43% of the patients were mildly depressed and mainly male patients. Zung score was correlated with post-operative improvements in EQ-5D and arm and neck pain PROs.

Aims

The aim of this study was to compare the functional and radiological outcomes and the complication rate after nail and plate fixation of unstable fractures of the ankle in elderly patients.

Abstract

Aims

As a proven and comprehensive molecular technique, metagenomic next-generation sequencing (mNGS) has shown its potential in the diagnosis of pathogens in patients with periprosthetic joint infection (PJI), using a single type of specimen. However, the optimal use of mNGS in the management of PJI has not been explored. In this study, we evaluated the diagnostic value of mNGS using three types of specimen with the aim of achieving a better choice of specimen for mNGS in these patients.

Abstract

Aims

The purpose of our study was to determine whether mesenchymal stem cells (MSCs) are an effective and safe therapeutic agent for the treatment of knee osteoarthritis (OA), owing to their cartilage regeneration potential.

Aims

This study aimed to explore whether serum combined with synovial interleukin-6 (IL-6) measurement can improve the accuracy of prosthetic joint infection (PJI) diagnosis, and to establish the cut-off values of IL-6 in serum and synovial fluid in detecting chronic PJI.

Aims

The aims of this study were to validate the outcome of total elbow arthroplasty (TEA) in patients with rheumatoid arthritis (RA), and to identify factors that affect the outcome.

A novel injectable hydrogel based on DNA and silicate nanodisks was fabricated and optimized to obtain a suitable drug delivery platform for biomedical applications. Precisely, the hydrogel was designed by combining two different type of networks: a first network (type A) made of interconnections between neighboring DNA strands and a second one (type B) consisting of electrostatic interactions between the silicate nanodisks and the DNA backbone. The silicate nanodisks were introduced to increase the viscosity of the DNA physical hydrogel and improve their shear-thinning properties. Additionally, the silicate nanodisks were selected to modulate the release capability of the designed network.

DNA 4% solutions were heated at 90°C for 45 seconds and cooled down at 37°C degree for two hours. In the second step, the silicate nanodisks suspension in water at different concentrations (0.1 up to 0.5%) were then mixed with the pre-gel DNA hydrogels to obtain the nanocomposite hydrogels. Rheological studies were carried out to investigate the shear thinning properties of the hydrogels. Additionally, the hydrogels were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron microscopy. The hydrogels were loaded with the osteoinductive drug dexamethasone and its release was tested in vitro in phosphate buffer pH 7.4. The drug activity upon release was tested evaluating the osteogenic differentiation of human adipose derived stem cells (hASCs) in vitro through analysis of main osteogenic markers and quantification of alkaline phosphatase activity and calcium deposition. Finally, the hydrogels were tested in vivo and injected into cranial defects in rats to assess their biocompatibility and bone regeneration potential.

The inclusion of the silicate nanodisks increased the viscosity of the hydrogels and the best results were obtained with the highest concentration of the nanoclay (0.5%). The hydrogels possessed shear-thinning properties as demonstrated by cyclic strain sweep tests and were able to recover their original storage modulus G' upon removal of strain. Such improvement in the injectable properties of the formulated hydrogels was mainly attributed to the formation of electrostatic interactions between the silicate nanodisks and the phosphate groups of the DNA backbone as confirmed by XPS analysis of the O, N, and P spectra. Additionally, laponite was able to sustain the release of the osteoinductive drug dexamethasone which was instead completely released from the DNA-based hydrogels after a week. The drug after being released was still active and promoted the osteogenic differentiation of hASCs as confirmed by ALP expression and expression of main osteogenic markers including ALP and COLA1. Finally, the gels proved to be biocompatible in vivo when injected into cranial defects and promoted bone formation at the periphery of the defect after a month post-treatment.

A novel injectable shear-thinning DNA-based hydrogel was characterized and tested for its drug delivery properties. The hydrogel can promote the sustain release of a small molecule like dexamethasone and be biocompatible in vitro and in vivo. Due to these promising findings, the designed system could find also applicability for the delivery of growth factors or other therapeutic molecules.

Previous study reported that intra-articular injection of MgSO4 could alleviate pain related behaviors in a collagenase induced OA model in rats. It provided us a good description on the potential of Mg2+ in OA treatment. However, the specific efficiency of Mg2+ on OA needs to be further explored and confirmed. The underlying mechanisms should be elucidated as well. Increasing attention has been paid on existence of synovial fluid MSCs (SF-MSCs) (not culture expanded) which may participate in endogenous reparative capabilities of the joint. On the other hand, previous studies demonstrated that Mg2+ not only promoted the expression of integrins but also enhanced the strength of fibronectin-integrin bonds that indicated the promotive effect of Mg2+ on cell adhesion, moreover, Mg2+ was proved could enhance chondrogenic differentiation of synovial membrane derived MSCs by modulating integrins. Based on these evidence, we hypothesize herein intra-articular injection of Mg2+ can attenuate cartilage degeneration in OA rat through modulating the biological behavior of SF-MSCs.

Human and rat SF-MSCs were collected after obtaining Experimental Ethics approval. The biological behaviors of both human and rat SF-MSCs including multiple differentiation, adhesion, colony forming, proliferation, etc. were determined in vitro in presence or absence of Mg2+ (10 mmol/L). Male SD rats (body weight: 450–500 g) were used to establish anterior cruciate ligament transection and partial medial meniscectomy (ACLT+PMM) OA models. The rats received ACLT+PMM were randomly divided into saline (control) group and MgCl2 (0.5 mol/L) group (n=6 per group). Intra-articular injection was performed on week 4 post-operation, twice per week for two weeks. Knee samples were harvested on week 2, 4, 8, 12 and 16 after injection for histological analysis for assessing the progression of OA. On week 2 and 4 after injection, the rat SF-MSCs were also isolated before the rats were sacrificed for assessing the abilities of chondrogenic differentiation, colony forming and adhesion in vitro. Statistical analysis was done using Graphpad Prism 6.01. Unpaired t test was used to compare the difference between groups. Significant difference was determined at P < 0 .05.

The adhesion and chondrogenic differentiation ability of both human and rat SF-MSCs were significantly enhanced by Mg2+ (10 mmol/L) supplementation in vitro. However, no significant effects of Mg2+ (10 mmol/L) on the osteogenic and adipogenic differentiation as well as the colony forming and proliferation. In the animal study, histological analysis by Saffranin O and Toluidine Blue indicated the cartilage degeneration was significantly alleviated by intra-articular injection of Mg2+, in addition, the expression of Col2 in cartilage was also increased in MgCl2 group with respect to control group indicated by immunohistochemistry. Moreover, the OARSI scoring was decreased in MgCl2 group as well. Histological analysis and RT-qPCR indicated that the chondrogenic differentiation of SF-MSCs isolated from Mg2+ treated rats were significantly enhanced compare to control group.

In the current study, we have provided direct evidence supporting that Mg2+ attenuated the progression of OA. Except for the effect of Mg2+ on preventing cartilage degeneration had been demonstrated in this study, for the first time, we demonstrated the promoting effect of Mg2+ on adhesion and chondrogenic differentiation of endogenous SF-MSCs within knee joint that may favorite cartilage repair. We have confirmed that the anti-osteoarthritic effect of Mg2+ involves the multiple actions which refer to prevent cartilage degeneration plus enhance the adhesion and chondrogenic differentiation of SF-MSCs in knee joint to attenuate the progression of OA. These multiple actions of Mg2+ may be more advantage than traditional products. Besides, this simple, widely available and inexpensive administration of Mg2+ has the potential on reducing the massive heath economic burden of OA. However, the current data just provided a very basic concept, the exact functions and underlying mechanisms of Mg2+ on attenuating OA progression still need to be further explored both in vitro and in vivo. Formula of Mg2+ containing solution also need to be optimized, for example, a sustained and controlled release delivery system need to be developed for improving the long-term efficacy.

Patellar fractures account for approximately 1% of all fractures. Open reduction and internal fixation is recommended to restore extensor continuity and articular congruity. However, complications such as nonunion and symptomatic hardware, still exist. Furthermore, there is a risk of re-fracturing of the healed bone during the removal of the implants. Magnesium (Mg), a biodegradable metal, has elastic moduli and compressive yield strength that are comparable to those of natural bone. Our previous study showed that released Mg ions enhanced fracture healing. However, Mg-based implants degrade rapidly after implantation and lead to insufficient mechanical strength to support the fracture. Microarc oxidation (MAO) is a metal surface coating that reduces corrosion. We hypothesized that Mg pins, with or without MAO, would enhance fracture healing radiologically, mechanically, and histologically, while MAO would decrease degradation of Mg pins.

Patellar fracture was performed on forty-eight 18-week-old female New Zealand White rabbits according to established protocol. Briefly, the patella is osteotomized transversely and a tunnel (1.1mm) was drilled longitudinally through the two bone fragments. A pin (1 mm, stainless steel, Mg, or MAO-Mg) was inserted into the tunnel. The reduced construct was stabilized with a figure-of-eight band wire (⊘ 0.6 mm stainless steel wire). Cast immobilization was applied for 6 weeks. The rabbits were euthanized at week 8 and 12 post-operation. Microarchitecture and mechanical properties of the repaired patella were analyzed with microCT and tensile testing respectively. Histological sections of the repaired patella were stained. To evaluate the effect of the MAO treatment on degradation rate of Mg pin, the volume of the Mg pins in the patella was measured with microCT.

At week 8, both Mg and Mg-MAO showed higher ratio of bone volume to tissue volume (BV/TV) than the control while there was no significant different between Mg and Mg-MAO. At week 12, Control, Mg, and Mg-MAO groups showed enlarged patella when compared to the normal patella. Tissue volume (TV) and bone volume (BV) of the patella in Mg and Mg-MAO were larger than those in the Control group. However, the Control had higher ratio of bone volume to tissue volume (BV/TV), TV density, and BV density than Mg and Mg-MAO. Tensile testing showed that the mechanical properties of the repaired patella (failure load, stiffness, ultimate strength, and energy-to-failure) of Mg and Mg-MAO were higher than that of the control at both week 8 and week 12. Histological analysis showed that there was significant new bone formation in the Mg and Mg-MAO group compared with the Control group at week 8 and 12. The degradation rate of the MAO-coated Mg pins was significantly slower than those without MAO at week 8 but no significant difference was detected at week 12.

Mechanical, microarchitectural, and histological assessments showed that Mg pins, with or without MAO, enhanced fracture healing of the repaired patella compared to the Control. MAO treatment enhanced the corrosion resistance of the Mg pins at the early time point.

A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing.

Cite this article: Bone Joint Res 2020;9(7):368–385.

Ankle fractures are the fourth most common fracture requiring surgical management. The deltoid ligament is considered the primary stabilizer of the ankle against a valgus force. The management of the deltoid ligament in ankle fractures is currently a controversial topic no consensus exists regarding repair in the setting of ankle fractures. The purpose of this systematic review is to examine the role and indications for deltoid ligament repair in ankle fractures.

A systematic database search was conducted with Medline, Pubmed and Embase for relevant studies discussing patients with ankle fractures involving deltoid ligament rupture and repair. The papers were screened independently and in duplicate by two reviewers. Study quality was evaluated using the MINORs criteria. Data extraction included post-operative outcomes, pain, range of motion (ROM), function, medial clear space (MCS), syndesmotic malreduction and complication rates.

Following title, abstract and full text screening, 10 eligible studies published between 1987 and 2017 remained for data extraction (n = 528). The studies include 325 Weber B and 203 Weber C type fractures. Malreduction rate in studies with deltoid ligament repair was 7.4% in comparison to those without repair at 33.3% (p < 0.05). Eleven (4%) of deltoid ligament repair patients returned for re-operation to have implants removed in comparison to eighty three (42%) of those without repair (p < 0.05). There was no significant difference for pain, function, ROM, MCS and complication rates (p < 0.05). The mean operating time of deltoid ligament repair groups was 20 minutes longer than non-repair groups(p < 0.05).

Deltoid ligament repair offers significantly lower syndesmotic malreduction rates and reduced re-operation rates for hardware removal when performed instead of transsyndesmotic screw fixation. When compared to non-repair groups, there are no significant differences in pain, function, ROM, MCS and complication rates. Deltoid ligament repair should be considered for ankle fracture patients with syndesmotic injury, especially those with Weber C. Other alternative syndesmotic fixation methods such as suture button fixation should be explored. A large multi-patient randomized control trial is required to further examine the outcomes of ankle fracture patients with deltoid ligament repair.

Aims

Prosthetic joint infection (PJI) remains a major clinical challenge. Neutrophil CD64 index, Fc-gamma receptor 1 (FcγR1), plays an important role in mediating inflammation of bacterial infections and therefore could be a valuable biomarker for PJI. The aim of this study is to compare the neutrophil CD64 index in synovial and blood diagnostic ability with the standard clinical tests for discrimination PJI and aseptic implant failure.

Aims

To evaluate the donor site morbidity and tendon morphology after harvesting whole length, full-thickness peroneus longus tendon (PLT) proximal to the lateral malleolus for ligament reconstructions or tendon transfer.

Aims

The aim of this meta-analysis was to compare the outcome of total elbow arthroplasty (TEA) undertaken for rheumatoid arthritis (RA) with TEA performed for post-traumatic conditions with regard to implant failure, functional outcome, and perioperative complications.

Objectives

The optimal protocol for antibiotic loading in the articulating cement spacers for the treatment of prosthetic joint infection (PJI) remains controversial. The objective of the present study was to investigate the effectiveness of articulating cement spacers loaded with a new combination of antibiotics.

Objectives

The optimal protocol for antibiotic loading in the articulating cement spacers for the treatment of prosthetic joint infection (PJI) remains controversial. The objective of the present study was to investigate the effectiveness of articulating cement spacers loaded with a new combination of antibiotics.

Aims

The aim of this study was to evaluate the differences in revision and complication rates, functional outcomes, and radiological outcomes between cemented and press-fit humeral stems in primary anatomical total shoulder arthroplasty (TSA).

Objectives

Adult mice lacking the transcription factor NFAT1 exhibit osteoarthritis (OA). The precise molecular mechanism for NFAT1 deficiency-induced osteoarthritic cartilage degradation remains to be clarified. This study aimed to investigate if NFAT1 protects articular cartilage (AC) against OA by directly regulating the transcription of specific catabolic and anabolic genes in articular chondrocytes.

Introduction

Self tapping bone screw has been widely used in the fixation of Arthroplasty implants and bone graft. But the unwanted screw or driver breakage can be a direct result of excessive driving torque due to the thread cutting resistance. Previous studies showed that bone drill bit cutting rake angle was a critical factor and was inversely related to the bone cutting efficiency.^{1, 2, 3, 4} (Figure 1) However to date there was no data for how the rake angle could influence the performance of self tapping bone screw. The purpose of this study was to investigate the torque generated by the self tapping cortical screw in simulated bone insertion as a function of the screw tip cutting flute rake angle.

Posterior cruciate ligament deficiency (PCLD) leads to structural and proprioceptive impairments of the knee, affecting the performance of daily activities including obstacle-crossing. Therefore, identifying the biomechanical deficits and/or strategies during this motor task would be helpful for rehabilitative and clinical management of such patients. A safe and successful obstacle-crossing requires stability of the body and sufficient foot clearance of the swing limb. Patients with PCLD may face demands different from normal when negotiating obstacles of different heights. The objective of this study was thus to identify the biomechanical deviations/strategies of the lower limbs in unilateral PCLD during obstacle-crossing using motion analysis techniques.

Twelve patients with unilateral PCLD and twelve healthy controls participated in the current study with informed written consent. They were asked to walk and cross obstacles of heights of 10%, 20% and 30% of their leg lengths at self-selected speeds. The PCLD group was asked to cross the obstacles with each of the affected and unaffected limb as the leading limb, denoted as PCLD-A and PCLD-U, respectively. The kinematic and kinetic data were measured with a 7-camera motion analysis system (Vicon, Oxford Metrics, U.K.) and two force plates (AMTI, U.S.A.). The angles of the stance and swing limbs (crossing angles) and the moments of the stance limbs (crossing moments) for each joint in the sagittal plane when the leading limb was above the obstacle were calculated for statistical analysis. A 3 by 2, 2-way mixed-model analysis of variance with one between-subject factor (PCLD-A vs. Control, and PCLD-U vs. Control) and one within-subject factor (obstacle height) was performed (α=0.05). Paired t-test was used to compare the variables between PCLD-A and PCLD-U (α=0.05). SAS version 9.2 was used for all statistical analysis.

When the leading toe was above the obstacle, the PCLD group showed significantly greater hip flexion in the swing limb but decreased dorsiflexion in the stance limb, both in PCLD-A and PCLD-U (P<0.05). Greater knee flexion and greater ankle dorsiflexion were found in the leading limb in PCLD-A (P<0.05). Meanwhile, the PCLD group showed significantly decreased ankle plantarflexor but increased knee extensor crossing moments in the stance limb compared with the Control (P<0.05). None of the calculated variables were found to be significantly different between PCLD-A and PCLD-U (P>0.05).

When crossing the obstacle, patients with PCLD reduced ankle plantarflexor moments that were mainly produced by the gastrocnemius. This may help reduce the posterior instability of the affected knee. Greater knee extensor crossing moments may also help reduce the posterior instability of the standing knee when the leading toe was above the obstacle.

The changed joint kinetics as a result of PCLD were not only seen on the affected side but also on the unaffected side during obstacle-crossing. This symmetrical pattern may be necessary in performing functional activities that may require either the affected side or the unaffected side leading. These results suggest that rehabilitative intervention, including muscular strengthening, on both affected and unaffected sides are necessary in patients with unilateral PCLD.

Introduction

Medial open wedge high tibial osteotomy (HTO) is a generally accepted surgical method for medial unicompartmental osteoarthritis with varus malalignment of the lower extremity. However, several authors have suggested the possibility of unintentional secondary changes during open wedge HTO, which include posterior tibial slope angle (PTS) change, tibial rotation change and medial–lateral slope change of the knee joint line, may influence knee kinematics and produce poor clinical outcomes. We sought to analyze postoperative changes in three-dimensional planes using a virtual wedge osteotomy 3D model. Pre- and post-operative changes in the medial proximal tibial angle (MPTA) in the coronal plane, posterior tibial slope (PTS) in the sagittal plane, and axial tibial rotation were measured as dependent variables. And this study was attempted to determine their mutual relationships and to clarify which independent variables, including hinge axis angle and gap ratio, affect tibial rotation change and PTS change by applying the identified hinge position.

Objective

The purpose of this study was to investigate how rim poly locking scallop cutting depth could affect the rigidity of acetabular cup.

Aims

The aim of this study is to introduce and investigate the efficacy and feasibility of a new vertebral osteotomy technique, vertebral column decancellation (VCD), for rigid thoracolumbar kyphotic deformity (TLKD) secondary to ankylosing spondylitis (AS).

PEEK rods construct has been proposed to allow better load sharing among spinal components when compared to the more traditional Titanium rods constructs. However, such proposal has largely derived from single-load in-vitro testing and the biomechanical differences between the two constructs when subjected to fatigue loading remain unknown. Current study comparatively analyzed the in-vitro biomechanical performance of PEEK and Titanium rod constructs as spinal implants through a 5 hour fatigue loading test. The disc height and intradiscal pressure of the instrumented and adjacent levels pre- and post-loading were recorded for analysis. The stress levels on the rods and bone stress near the screw-bone interface were also collected to investigate the likely failure rates of the two constructs. The results showed that the Titanium rods construct demonstrated a minimum amount of loss of disc height and intradiscal pressure at the instrumented level, however, a significant loss of the disc height and intradiscal pressure at adjacent levels compared to the intact spine were identified. In contrast, the disc height and intradiscal pressure of the PEEK rods were found to be comparable to those of the intact spine for all levels. The PEEK rods group also showed significantly less bone stress near the screw-bone interface compared to the Titanium rods group. Current study has demonstrated the potential benefits of the PEEK rods construct in reducing the risks of adjacent segment disease and implant failure rates when compared to the more traditional Titanium rods construct.

Tranexamic acid (TXA), an inhibitor of fibrinolysis, reduces blood loss after total knee arthroplasty. However, its effect on minimally invasive total hip arthroplasty (THA) is not clear. We performed a prospective, randomised double-blind study to evaluate the effect of two intravenous injections of TXA on blood loss in patients undergoing minimally invasive THA.

In total, 60 patients (35 women and 25 men with a mean age of 58.1 years; 17 to 84) who underwent unilateral minimally invasive uncemented THA were randomly divided into the study group (30 patients, 20 women and ten men with a mean age of 56.5 years; 17 to 79) that received two intravenous injections 1 g of TXA pre- and post-operatively (TXA group), and a placebo group (30 patients, 15 women and 15 men with a mean age of 59.5 years; 23 to 84). We compared the peri-operative blood loss of the two groups. Actual blood loss was calculated from the maximum reduction in the level of haemoglobin. All patients were followed clinically for the presence of venous thromboembolism.

The TXA group had a lower mean intra-operative blood loss of 441 ml (150 to 800) versus 615 ml (50 to 1580) in the placebo (p = 0.044), lower mean post-operative blood loss (285 ml (120 to 570) versus 392 ml (126 to 660) (p = 0.002), lower mean total blood loss (1070 ml (688 to 1478) versus 1337 ml (495 to 2238) (p = 0.004) and lower requirement for transfusion (p = 0.021). No patients in either group had symptoms of venous thromboembolism or wound complications.

This prospective, randomised controlled study showed that a regimen of two intravenous injections of 1 g TXA is effective for blood conservation after minimally invasive THA.

Cite this article: Bone Joint J 2015;97-B:905–10.

Summary Statement

Using the latest Next Generation Sequencing technologies, we have investigated miRNA expression profiles in human trabecular bone from total hip replacement (THR) revision surgery where wear particle associated osteolysis was evident.

Objectives

Femoral shaft fracture treatment often results in mal-alignment and the high dosage of radiation exposure. The objective of this study is to develop a Parallel Manipulator Robot (PMR) on traction table to overcome these difficulties so as achieve better alignment for the fractured femur and reduce radiation to both patients and physicians.

Objectives

Percutaneous iliosacral screw placement is a standard, stabilization technique for pelvic fractures. The purpose of this study was to assess the effectiveness of a novel biplanar robot navigation aiming system for percutaneous iliosacral screw placement in a human cadaver model.

Objective

Femoral shaft fracture treatment often results in mal-alignment and the high dosage of radiation exposure. The objective of this study is to develop a Parallel Manipulator Robot (PMR) on traction table to overcome these difficulties so as achieve better alignment for the fractured femur and reduce radiation to both patients and physicians.

Structural allografts may be used to manage uncontained bone defects in revision total knee replacement (TKR). However, the availability of cadaver grafts is limited in some areas of Asia. The aim of this study was to evaluate the mid-term outcome of the use of femoral head allografts for the reconstruction of uncontained defects in revision TKR, focusing on complications related to the graft.

We retrospectively reviewed 28 patients (30 TKRs) with Anderson Orthopaedic Research Institute (AORI) type 3 bone defects, who underwent revision using femoral head allografts and stemmed components. The mean number of femoral heads used was 1.7 (1 to 3). The allograft–host junctions were packed with cancellous autograft.

At a mean follow-up of 76 months (38 to 136) the mean American Knee Society knee score improved from 37.2 (17 to 60) pre-operatively to 90 (83 to 100) (p < 0.001). The mean function score improved from 26.5 (0 to 50) pre-operatively to 81 (60 to 100) (p < 0.001). All the grafts healed to the host bone. The mean time to healing of the graft was 6.6 months (4 to 16). There have been no complications of collapse of the graft, nonunion, infection or implant loosening. No revision surgery was required.

The use of femoral head allografts in conjunction with a stemmed component and autogenous bone graft in revision TKR in patients with uncontained bone defects resulted in a high rate of healing of the graft with minimal complications and a satisfactory outcome. Longer follow-up is needed to observe the evolution of the graft.

Cite this article: Bone Joint J 2013;95-B:643–8.

Tranexamic acid (TEA), an inhibitor of fibrinolysis, reduces blood loss after routine total knee replacement (TKR). However, controversy persists regarding the dosage and timing of administration of this drug during surgery. We performed a prospective randomised controlled study to examine the optimum blood-saving effect of TEA in minimally invasive TKR.

We randomly assigned 151 patients who underwent unilateral minimally invasive TKR to three groups: 1) a placebo group (50 patients); 2) a one-dose TEA group (52 patients), who received one injection of TEA (10 mg/kg) intra-operatively on deflation of the tourniquet; and 3) a two-dose TEA group (49 patients), who received two injections of TEA (10 mg/kg) given pre-operatively and intra-operatively. Total blood loss was calculated from the maximum loss of haemoglobin. All patients were followed clinically for the presence of venous thromboembolism (VTE).

The mean total blood loss was significantly higher in the placebo group than in the other two groups (1222 ml (845 to 2043) versus 1035 ml (397 to 1934) and 986 ml (542 to 1811), respectively (both p < 0.0001)). The mean blood loss was not significantly different between the one- and two-TEA groups (p = 0.148). The mean transfusion rate was higher in the placebo group than in the other two groups (22% versus 3.8% (p = 0.006) and 6.1% (p = 0.041), respectively) and there was no statistically significant difference in the mean transfusion rate between the one- and two-TEA groups (p = 0.672). Only one patient, in the two-dose group, had a radiologically confirmed deep venous thrombosis.

Our prospective randomised controlled study showed that one intra-operative injection of TEA is effective for blood conservation after minimally invasive TKR.

Intra-articular resection of bone with soft-tissue balancing and total knee replacement (TKR) has been described for the treatment of patients with severe osteoarthritis of the knee associated with an ipsilateral malunited femoral fracture. However, the extent to which deformity in the sagittal plane can be corrected has not been addressed. We treated 12 patients with severe arthritis of the knee and an extra-articular malunion of the femur by TKR with intra-articular resection of bone and soft-tissue balancing. The femora had a mean varus deformity of 16° (8° to 23°) in the coronal plane. There were seven recurvatum deformities with a mean angulation of 11° (6° to 15°) and five antecurvatum deformities with a mean angulation of 12° (6° to 15°).

The mean follow-up was 93 months (30 to 155). The median Knee Society knee and function scores improved from 18.7 (0 to 49) and 24.5 (10 to 50) points pre-operatively to 93 (83 to 100) and 90 (70 to 100) points at the time of the last follow-up, respectively. The mean mechanical axis of the knee improved from 22.6° of varus (15° to 27° pre-operatively to 1.5° of varus (3° of varus to 2° of valgus) at the last follow-up. The recurvatum deformities improved from a mean of 11° (6° to 15°) pre-operatively to 3° (0° to 6°) at the last follow-up. The antecurvatum deformities in the sagittal plane improved from a mean of 12° (6° to 16°) pre-operatively to 4.4° (0° to 8°) at the last follow-up.

Apart from varus deformities, TKR with intra-articular bone resection effectively corrected the extra-articular deformity of the femur in the presence of antecurvatum of up to 16° and recurvatum of up to 15°.

There has been concern over the safety of the upright position for shoulder surgery from anaesthetists uncomfortable with the risk of reduced cerebral blood flow (CBF). Because there are no studies documenting what happens to CBF during upright surgery we aimed to measure CBF through an indirect and non-invasive method using recently available Ultrasound monitoring equipment.

This study randomised patients into awake (interscalene block alone) and GA with block, and indirectly measured the CBF by using a validated Doppler technique on carotid flow both before and during the shoulder procedure. Non-invasive and invasive measurements of mean arterial pressure were made throughout the procedure, together with doppler measurement of carotid flow following preoperative measurement of carotid contribution to cerebral flow in the radiology department by an experienced sonographer. All measurements recorded in real time and charted independently.

This study has shown that CBF in both groups were consistent with the expected values, and CBF remained proportionate in supine to upright. CBF values in the block alone group were generally lower than the GA group. In the GA group the MAP dropped lower, requiring use of adrenergic drugs to bring the pressure up. Despite the significant drop in MAP, the CBF was still high. This could signify cerebral autoregulation is a significant factor in the upright position.

We have shown the feasibility of use of DOppler to indirectly measure CBF during upright surgery. Despite the predicted drop in MAP in this position with GA, we could NOT show a concurrent drop in CBF, demonstrating that much more complex factors regulate the CBF in these patients. Clearly, monitoring is the key to safe administration of anaesthetic in the upright position.

Platelet-leucocyte gel (PLG), a new biotechnological blood product, has hitherto been used primarily to treat chronic ulcers and to promote soft-tissue and bone regeneration in a wide range of medical fields. In this study, the antimicrobial efficacy of PLG against Staphylococcus aureus (ATCC 25923) was investigated in a rabbit model of osteomyelitis. Autologous PLG was injected into the tibial canal after inoculation with Staph. aureus. The prophylactic efficacy of PLG was evaluated by microbiological, radiological and histological examination. Animal groups included a treatment group that received systemic cefazolin and a control group that received no treatment.

Treatment with PLG or cefazolin significantly reduced radiological and histological severity scores compared to the control group. This result was confirmed by a significant reduction in the infection rate and the number of viable bacteria. Although not comparable to cefazolin, PLG exhibited antimicrobial efficacy in vivo and therefore represents a novel strategy to prevent bone infection in humans.

Purpose: Published series of minimally invasive cervical foraminotomy (MICF) have shown excellent short-term relief of cervical radiculopathy (85–98%) with minimal surgical morbidity. There have been no long-term clinical series documenting the stability of these results over time. This is the first long-term follow-up of MICF patients to determine the incidence of recurrent symptoms and need for additional cervical spine surgery.

Methods: We conducted a multi-center retrospective chart review of 73 patients who had MICF. Clinical outcome measures were assessed from clinic records, operative records, and telephone surveys.

Results: At 3 months, 70/73 patients (96%) reported relief of radicular pain compared to their preoperative state. By 40 months, 15 patients reported symptoms of cervical radiculopathy. 8 patients experienced recurrent symptoms, and the remaining 7 had a new radicular pattern. Of 7 patients with symptoms at new levels, 6 had pre-existing radiographic abnormality. 15 patients underwent additional cervical surgery after MICF. 3 patients underwent repeat MICF at the same level. An additional 2 patients had MICF at a different level. 7 patients had ACDF at the same level and 2 had fusion at a different level. There were no cases of frank instability or spondylolisthesis noted.

Conclusions: At 40 month follow-up, 21% or patients had radicular symptoms with 11% reporting recurrence of preoperative symptoms and 9% with radicular symptoms in a different distribution. 12% (9/73 patients) of the group required ACDF within the follow-up period. Thus, 64/73 patients were spared fusion in this series. Assuming the 2.5% per year incidence of adjacent level fusion cited in the literature, there would have been 6 cases likely to have required another fusion if all 73 patients had been treated with ACDF initially. From this perspective, MICF continues to be our procedure of choice for properly selected patients with cervical radiculopathy.

Background: Aseptic loosening remains the most common cause of failure of total hip arthroplasty. Its pathogenesis is based upon the generation of wear debris particles which trigger synovial macrophage activation.

Statins, inhibitors of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-Co-A) reductase, have revolutionised the treatment of hypercholesterolaemia. More recently statins have been shown to have potent anti inflammatory effects. We investigated the effects of cerivastatin in attenuating the activation of human macrophages by polymethylmethacrylate (PMMA) particles.

Methods: Polymethylmethacrylate-particle-stimulated human macrophages were cultured in vitro with cerivastatin at 75 and 150... mols/litre. TNF-α (tumour necrosis factor alpha) and MCP-1 (monocyte chemotactic protein) expression were determined using ELISA. An ERK1/2 inhibitor, UO126 was utilised to identify the mitogen activated protein kinase (MAP-Kinase) pathway involved and western blotting was used to demonstrate the effect of Cerivastatin on this pathway.

Results PMMA-stimulated TNF-α and MCP-1 expression was consistently attenuated by cerivastatin therapy.

PMMA activation was attenuated by the ERK1/2 inhibitor, UO126.

Western blotting confirmed ERK downregulation by cerivastatin, establishing a mechanism for its anti-inflammatory effects.

Conclusion: We have demonstrated the beneficial effects of statins in suppressing particle mediated activation of macrophages and the potential to prevent or treat periprosthetic osteolysis.

Failure of total hip arthroplasty with acetabular deficiency occurred in 55 patients (60 hips) and was treated with acetabular revision using morsellised allograft and a cemented metal-backed component. A total of 50 patients (55 hips) were available for clinical and radiological evaluation at a mean follow-up of 5.8 years (3 to 9.5). No hip required further revision of the acetabular component because of aseptic loosening.

All the hips except one had complete incorporation of the allograft demonstrated on the radiographs. A complete radiolucent line of > 1 mm was noted in two hips post-operatively. A good to excellent result occurred in 50 hips (91%). With radiological evidence of aseptic loosening of the acetabular component as the end-point, the survivorship at a mean of 5.8 years after surgery was 96.4%.

The use of impacted allograft chips in combination with a cemented metal-backed acetabular component and screw fixation can achieve good medium-term results in patients with acetabular bone deficiency.

Background: Periprosthetic osteolysis precipitates aseptic component loosening, increases periprosthetic fracture risk and through massive bone loss, complicates revision surgery.

Its pathogenesis is based upon the generation of wear debris particles which trigger synovial macrophage activation. Statins, inhibitors of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-Co-A) reductase, have revolutionised the treatment of hypercholesterolaemia and cardiovascular disease. The antiinflammatory properties of HMG-CoA reductase inhihitors or the statin family are well recognised. We investigated the effects of ceriv-astatin in attenuating the activation of human macrophages by polymethylmethacrylate (PMMA) particles.

Methods: Polymethylmethacrylate-particle-stimulated human macrophages were cultured in vitro with cerivastatin at 75 and 150micromols/litre. TNF- alpha (tumour necrosis factor alpha) and MCP-1 (monocyte chemotactic protein) expression were determined using ELISA. UO126, a Raf/MEK/ERK intracellular transduction pathway inhibitor, was utilised to identify the mitogen activated protein kinase (MAP- Kinase) pathway involved and western blotting was used to demonstrate the effect of cerivastatin on this pathway.

Results Human monocyte/macrophage cultures were activated by PMMA particles evidenced by TNF- alpha and MCP-1 expression(p< 0.05). This activation was consistently attenuated by cerivastatin therapy. Similarily, PMMA activation was attenuated by the Raf/MEK/ERK inhibitor, UO126.

Western blotting confirmed Raf/MEK/ERK down-regulation by cerivastatin, establishing a mechanism for its anti-inflammatory effects.

Conclusion We have demonstrated in vitro, that statins can abrogate particle induced inflammatory responses in a dose dependent manner and this is mediated intra-cellularily through its effect on the Raf/MEK/ERK transduction pathway. We propose that by attenuating this inflammatory response, the associated subsequent osteoclast activation and osteolysis is attenuated. Statins therefore may have role in promoting implant longevity

Background Apoptosis of osteoblasts and osteoclasts regulates bone homeostasis. Skeletal injury in humans results in angiogenic responses primarily mediated by vascular endothelial growth factor(VEGF), a protein essential for bone repair in animal models. Osteoblasts release VEGF in response to a number of stimuli and express receptors for VEGF in a differentiation dependent manner. This study investigates the putative role of VEGF in regulating the lifespan of primary human osteoblasts(PHOB) in vitro.

Methods PHOB were examined for VEGF receptors. Cultures were supplemented with VEGF(0–50ng/mL), a neutralising antibody to VEGF, mAB VEGF(0.3ug/mL) and Placental Growth Factor (PlGF), an Flt-1 receptor-specific VEGF ligand(0–100 ng/mL) to examine their effects on mineralised nodule assay, alkaline phosphatase assay and apoptosis.. The role of the VEGF specific antiapoptotic gene target BCl2 in apoptosis was determined.

Results PHOB expressed functional VEGF receptors. VEGF 10 and 25 ng/mL increased nodule formation 2.3- and 3.16-fold and alkaline phosphatase release 2.6 and 4.1-fold respectively while 0.3ug/mL of mAB VEGF resulted in approx 40% reductions in both. PlGF 50ng/mL had greater effects on alkaline phosphatase release (103% increase) than on nodule formation (57% increase). 10ng/mL of VEGF inhibited spontaneous and pathological apoptosis by 83.6% and 71% respectively, while PlGF had no significant effect. Pretreatment with mAB VEGF, in the absence of exogenous VEGF resulted in a significant increase in apoptosis (14 vs 3%). BCl2 transfection gave a 0.9% apoptotic rate. VEGF 10 ng/mL increased BCl2 expression 4 fold while mAB VEGF decreased it by over 50%.

Conclusions VEGF is a potent regulator of osteoblast lifespan in vitro. This autocrine feedback regulates survival of these cells, mediated via the KDR receptor and expression of BCl2 antiapoptotic gene.

Aims: Pharmacological modulation of skeletal muscle reperfusion injury after trauma associated ischaemia may improve limb salvage rates and prevent the associated systemic sequelae. Resuscitation with hypertonic saline restores the circulating volume and has favourable effects on tissue perfusion and blood pressure. The purpose of our study was to evaluate the effects of hypertonic saline on skeletal muscle ischaemia reperfusion (I/R) injury and the associated endorgan injury.

Methods: Adult male Sprague Dawley rats (n=24) were randomised into three groups: control group, I/R group treated with normal saline and I/R group treated with hypertonic saline. Bilateral hind-limb ischaemia was induced by rubber band application proximal to the level of the greater trochanters for 2.5 hours. Treatment groups received either normal saline or hypertonic saline prior to tourniquet release. Following twelve hours reperfusion, the tibialis anterior muscle was dissected and muscle function assessed electrophysiologically by electrical field stimulation. The animals were then sacrificed and skeletal muscle harvested for evaluation. Lung tissue was also harvested for measurement of wet-to-dry ratio, myeloperoxidase content and histological analysis.

Results: Hypertonic saline significantly attenuated skeletal muscle reperfusion injury as shown by reduced twitch and tetanic contractions of the skeletal muscle (Table). There was also a significant reduction in lung injury as demonstrated by differences in wet-to-dry ratio, myeloperoxidase content and histological analysis.

Conclusion: Resuscitation with hypertonic saline may have a protective role in attenuating skeletal muscle ischaemia reperfusion injury and its associated systemic sequelae.

Introduction Structure, position, strength, function and durability are critical following reconstruction after treatment of bone tumours. We aimed to assess performance and make recommendations in relation to shoulder reconstruction.

Methods Shoulder reconstruction following resection of bone tumours of the shoulder girdle was evaluated for thirty-two patients treated from 1987 to 2002. Several kinds of reconstructive procedures were performed and classified according to the system of the Musculoskeletal Tumour Society. Fourteen patients had an osteosarcoma, ten patients had a chondrosarcoma, four patients had an Ewings sarcoma and four had an extensive giant-cell tumour. The choice of reconstruction depended on the type of resection and the needs of the patient. The functional results were assessed and graded quantitatively according to the functional rating system of the Musculoskeletal Tumor Society. The average duration of follow-up was 75 months for the 23 patients who were still alive at the time of the latest follow-up examination.

Results Nine patients died of malignancy (four patients with surgical stage III disease and one with Paget’s osteosarcoma); these patients had an average 18 months follow-up post-operatively. The resection was classified as wide in 27 of 32 patients and as marginal in five. Two patients had local recurrence. Functional results were related to the type of resection and the method of shoulder reconstruction. In patients where the deltoid and rotator cuff could be preserved, allograft-prosthetic composite had better function than prosthesis alone after intra-articular resection of the humerus because reconstruction of the deltoid and the rotator cuff could be performed incorporating the allograft. After intra-articular resection of the proximal humerus with loss of the abductor mechanism, arthrodesis resulted in good function and more strength than was found after reconstruction with prosthesis or allograft-prosthetic composite. A secondary arthrodesis was performed in two patients with symptomatic instability following failed reconstruction with an allograft-prosthetic composite or an osteoarticular allograft. Insertion of an allograft, a vascularized fibular graft, a rotational latissimus dorsi flap and cancellous autograft bone was the preferred arthrodesis technique to achieve fusion as well as to reduce complications. There was one fracture and one infection in 10 patients. After extra-articular resection of the glenoid cavity and the proximal humerus with abductor mechanism, reconstruction with a functional spacer frequently resulted in superior subluxation of the implant and only fair function of the shoulder. With two teen-aged patients, a free fibular graft inserted after intra-articular resection of the proximal humerus led to fair function, to be followed by secondary arthrodesis when growth is complete. After resection of the acromion-glenoid cavity complex in one patient and the entire scapula in a child, no reconstruction resulted in good function of the shoulder.

Conclusions Indications for the method of reconstruction depend on type of resection, age, gender, occupation, the expected functional level and restriction of activity. After resection of the abductor mechanism, arthrodesis resulted in more strength and capacity to position the arm in space. It was suitable for the young. Allograft-prosthetic composite showed better function when the abductor mechanism had been reconstructed. Prostheses should be used in old patients or for palliative surgical treatment after resection the abductor mechanism. The most durable and functional reconstruction was arthrodesis.

Aims: Circulating endothelial precursor cells (CEPs) are thought to play a role in angiogenesis. We investigated the angiogenic stress of musculoskeletal trauma on CEP kinetics in trauma patients and their bone marrow progenitor populations in a murine model. Methods: Peripheral blood mononuclear cells (PB-MNCs) were isolated from patients (n=12) on consecutive days following closed lower-limb diaphyseal fractures. CEP levels, deþned by the surface expression patterns of VEGFR2, CD34 and AC133 were determined and cytokine analysis of collected serum was performed. Bonemarrow precursors deþned byLy-6A/E and c-Kit expression were harvested following the traumatic insult from the murine model and quantiþed on ßow cytometry. Human and murine progenitor populations were cultured on þbronectin and examined for markers of endothelial cell lineage (Ulexeuropaeus- agglutinin-1 binding and acetylated-LDL uptake) and cell morphology. Statistical analysis was performed using variance analysis. Results: A consistent increase in human CEPs levels was noted within 72 hours of the initial insult, the percentage increase over day 1 reaching 300% (p=0.008) and returning to normal levels by day 10. Murine bone marrow precursors were mobilisd within 24 hrs peaking at 48hrs (900% p=0.035). On culture, morphologically characteristic endotheliallike cells binding UEA-1 and incorporating LDL were identiþed. Serum VEGF levels increased signiþcantly within 24 hrs of the insult, (p=0.018) preceeding the peak in CEP mobilisation. Conclusion: We propose that musculoskeletal trauma through the release of chemokines such as VEGF, promotes rapid mobilisation of CEPs from born marrow, which have the potential to contribute to reparative neovascularisation. Strategies to enhance CEPs kinetics may accelerate this process and offer a therapeutic role in aberrant fracture healing.