Introduction. The management of open long bone fractures is well described and has been standardised through a number of well-established guidelines. However, there is no consensus regarding the application of local antibiotics into the open fracture site as a means of reducing infection rates. Materials & Methods. A systematic review and meta-analysis were undertaken as per PRISMA guidelines. PROSPERO Registration CRD42022323545. PubMed, EMBASE, Scopus and CENTRAL were the databases assessed. The Newcastle Ottawa Scale and the Rob 2 Tool were used to assess bias. A qualitative synthesis of all included studies and meta-analysis of suitable subgroups was undertaken. Results. In total, 12 studies (11 observational, 1 RCT) assessing 2431 open fractures were included for analysis. All compared the addition of a local antibiotic therapy to a standard treatment versus the standard treatment alone. The methods of delivery were vancomycin powder (4 papers), tobramycin polymethylmethacrylate beads (4 papers), gentamicin coated intramedullary (IM) nails (2 papers), gentamicin injections (1 paper) and antibiotic released IM core cement (1 paper). The addition of vancomycin powder did not decrease infection rates in comparison to intravenous antibiotics alone (OR 1.3, 95% CI (0.75 – 2.26)). Antibiotic coated IM Nails appear to have an association with lower infection rates than standard IM Nails. PMMA antibiotics have shown varied results in reducing infection rates depending on the individual studies. Conclusions. There are numerous methods available to deliver antibiotics locally to an open fracture site. Further high-quality research is required to provide a definitive conclusion on their efficacy irrespective of delivery method

Open tibia fractures are common injuries in our paediatric population and are often associated with high-energy trauma such as pedestrian-vehicle accidents. At our institution, these injuries are routinely treated with debridement and mono-lateral external fixation. The purpose of this study was to determine the outcome of open tibia fractures treated according to this protocol, as well as the complication rate and factors contributing to the development of complications. We performed a retrospective folder review of all patients with open tibia fractures that were treated according to our protocol from 2015–2019. Patients treated by other means, who received primary treatment elsewhere, and with insufficient data, were excluded. Data was collected on presenting demographics, injury characteristics, management, and clinical course. Complications were defined as pin tract infections, delayed- or non-union, malunion, growth arrest, and neurovascular injury. Appropriate statistical analysis was performed. One-hundred-and-fifteen fractures in 114 children (82 males) with a median age of 7 years (IQR 6–9) were included in the analysis. Pedestrian vehicle accidents (PVA's) accounted for 101 (88%) of fractures, and the tibial diaphysis was affected in 74 cases (64%). Fracture severity was equally distributed among the Gustillo-Anderson grades. The median Abbreviated Injury Score was 4 (IQR 4;5). Ninety-five fractures (83%) progressed to uneventful union within 7 weeks. Twenty patients (17%) developed complications, with delayed union and fracture site infections being the most common complications. Gustillo-Anderson Grade 3 fractures, an increased Abbreviated Injury Score, and the need for advanced wound closure techniques were risk factors for developing complications. Surgical debridement and external fixation in a simple mono-lateral frame is an effective treatment for open tibia fractures in children and good outcomes were seen in 83% of patients. More severe injuries requiring advanced wound closure were associated with the development of complications

Abstract. Introduction. Vitamin D deficiency in the UK is well documented − 30–40% of the population. It is an essential component of calcium metabolism and adequate levels are important for bone healing. Studies have demonstrated an overall prevalence of vitamin D deficiency/insufficiency at 77% in trauma patients aged >18, deficiency alone was 39%. Adequate vitamin D levels have a positive effect on bone mineral density and callus formation at fracture sites. Methods. We conducted a retrospective consecutive case series of all patients aged 0–50 undergoing surgical management for any fracture in October 2021 to March 2022. We assessed if vitamin D levels were checked and if patients were prescribed replacement as per local guidelines. Results. A total of 131 patients were identified, (mean 29 years; 83 male and 48 female). Most cases were upper limb fractures (n=78, 60%), as opposed to lower limb (n=53, 40%). Only 20 (15%) had their levels checked, of which 13 (65%) were insufficient/deficient (10 insufficiency, 2 deficiency, 1 severe deficiency). Of these 13 patients, only 3 (23%) were prescribed replacement therapy. Conclusions. Only a small proportion of patients had their levels checked, however the majority were insufficient/deficient. The prevalence in our study is consistent with larger epidemiology studies, which reflect a higher rate of deficiency in fracture patients compared to the general population. Thus, we propose that all patients in this age group should undergo a vitamin d level check upon time of clerking and this should be accurately treated as per trust guidance

Introduction. Continuous compression implants (CCIs) are small memory alloy bone staples that can provide continuous compression across a fracture site, which change shape due to temperature changes. Reviews of CCIs in orthopaedics have documented their use in mainly foot and ankle surgery, with very limited descriptions in trauma. They could be beneficial in the management of complex or open injuries due to their low profile and quick insertion time. The aim of this case series were to clarify the use of CCIs in modern day limb reconstruction practice. Materials & Methods. This was a single centred study looking retrospectively at prospective data for patients who were treated for an acute fracture or non-union with a CCI between September 2019 and May 2023. Primary outcome was to determine the function and indication of the CCI as judged retrospectively and secondary outcomes investigated unplanned returns to theatre for infection or CCI failure. Results. Sixty patients were eligible with a mean age of 44.2 (range 8–89). Fifty-one patients were treated for acute fractures, nine for non-unions; and almost half (27 patients) had open injuries. There were seven different sites for treatment with a CCI, the most common being tibia (25 patients) and humerus (14 patients). Of the 122 CCIs used, 80 were used as adjuncts for fixation in 48 patients. Their indication as an adjunct fell into three distrinct categories – reduction of fracture (39 CCIs), fixation of key fragments (38 CCIs) and compression (3 CCIs). Of these 48 patients, 4 patients had a frame fixation, 19 had a nail fixation, 24 patients had a plate fixation. Forty-two CCIs were used in isolation as definitive fixation, all were for midfoot dislocations expect an open iliac wing fixation from a machete attack and an isolated paediatric medial malleolus fixation. Two patients returned to theatre for infection and two due to CCI failure. Conclusions. This series has demonstrated the versality of CCIs across multiple sites of the body and for a large variety of injuries. It has identified, when not used in isolation, three main indications to support traditional orthopaedic fixations. Given the unpredictability in limb reconstruction surgery, the diversity and potential of CCIs could form part of the staple diet in the modern-day practice

Introduction. Treatment of non-union in open tibial fractures Gustilo-Anderson(GA)-3A/3B fractures remains a challenging problem. Most of these can be dealt using treatment methods that requires excision of the non-union followed by bone grafting, masquelet technique, or acute shortening. Circular fixators with closed distraction or bone transport also remains a useful option. However, sometimes due to patient specific factors these cannot be used. Recently antibiotic loaded bone substitutes have been increasingly used for repairing infected non-unions. They provide local antibiotic delivery, fill dead space, and act as a bone conductive implant, which is resorted at the end of a few months. We aimed to assess the outcome of percutaneous injection of bone substitute while treating non-union of complex open tibial fractures. Materials & Methods. Three cases of clinical and radiological stiff tibial non-union requiring further intervention were identified from our major trauma open fracture database. Two GA-3B cases, treated with a circular frame developed fracture-related-infection(FRI) manifesting as local cellulitis, loosened infected wires/pins with raised blood-markers, and one case of GA-3A treated with an intramedullary nail. At the time of removal of metalwork/frame, informed consent was obtained and Cerament-G. TM. (bone-substitute with gentamicin) was percutaneously injected through a small cortical window using a bone biopsy(Jamshedi needle). All patients were allowed to weight bear as tolerated in a well-fitting air-cast boot and using crutches. They were followed up at 6 weekly intervals with clinical assessment of their symptoms and radiographs. Fracture union was assessed using serial radiographs with healing defined as filling of fracture gap, bridging callus and clinical assessment including return to full painless weight bearing. Results. Follow-up at 6 months showed all fractures had healed with no defect or gaps with evidence of new trabecular bone and significant resorption of Cerament-G. TM. at final follow-up. There was no evidence of residual infection with restoration of normal limb function. Fractures with no internal fixation showed a mild deformity that had developed during the course of the healing, presumed due to mild collapse in the absence of fixation. These were less than 10 degrees in sagittal and coronal planes and were clinically felt to be insignificant by the patients. Conclusions. Cerament-G's unique combination of high dose antibiotics and hydroxy apatite matrix provided by calcium sulphate might help provide an osteoconductive environment to allow these stiff non-unions to heal. The matrix appears to provide a scaffold-like structure that allows new bone in-growth with local release of antibiotics helping reduce deep-seated infections. The final deformation at fracture site underlines the need for fixation- and it is very unlikely that this technique will work in mobile nonunions. Whilst similar fractures may heal without the use of bone substitute injections, the speed of healing in presence of significant fracture gap suggests the use of these bone substitutes did help in our cases. Further studies with a larger cohort, including RCTs, to evaluate the effectiveness of this technique compared to other methods are needed

Abstract. A study was done to test the strength of various configurations of tension band wiring (TBW) and we report clinical results of ‘Horizontal Figure of Eight TBW’ (H – 8 TBW). In an experimental lab, a model of the fractured patella was mounted on a Nene tensile testing machine and various configurations of TBWs were tested in different positions of Kirschner wires. The strength of TBW and various knots securing the ends of wires were analysed on load/displacement graphs. The experimental results were compared with the theoretical results using trigonometry and mathematical equations. Since 1986, H – 8 TBW (Sonanis and Bhende modification) was used clinically in 42 patients (40 fractured patella, and 2 greater trochanteric osteotomies) in 26 males and 16 females and all patients were followed up to average 18 months. Experimentally H – 8 TBW (0.8mm wire) could resist maximum distraction force of 700 N and achieved maximum compression. Placement of the two Kirschner wires at the mid way between centre and edge of patella at the level of fracture site achieved optimum rotational stability and compression. Crimping method of gripping the ends of wires was the most secured method (120 N). Clinically bony union using H-8 TBW was achieved in all 41 patients. Complications seen were wire discomfort in 3 patients and one death. We conclude that H – 8 TBW achieved maximum compression, optimum K wire placement was at the 1/4th distance from the edge of the patella, and crimping the ends of wire secured best fixation

Aim. Staphylococcus aureus is the leading pathogen in fracture-related infection (FRI). Virulence factors vary between different strains, which may have a decisive influence on the course of infection. Previous in vitro experiments, in vivo testing in wax moth larvae, and genomic analysis of S. aureus isolates from FRI identified a low- and high-virulent strain. These findings correlated with the acute course of FRI induced by the high-virulent pathogen, whereas the low-virulent strain caused a chronic FRI in its human host. However, the role of bacterial virulence in FRI is not completely understood. Therefore, the present study aimed to compare the identified high- and low-virulent S. aureus isolates in a murine FRI model. Method. Skeletally mature C57Bl/6N mice received a femoral osteotomy stabilized by titanium locking plates. FRI was established by inoculation of either high-virulent S. aureus EDCC 5458 or low-virulent S. aureus EDCC 5464 in the fracture gap. Mice were euthanized 4 and 14 days after surgery, respectively. Severity and progression of infection were assessed in terms of clinical presentation, quantitative bacteriology, semiquantitative histopathologic evaluation, and serum cytokine profile. Results. Quantitative bacteriological results 4 days after surgery revealed a higher bacterial load in soft tissue samples in high-virulent infected animals (p =0.026). Mice infected with the high-virulent strain also displayed higher rates of organ dissemination (24/36 organs in high-virulent, versus 5/36 organs in low-virulent infected animals; p <0.0001). In the histopathological assessment, bacterial agglomerations at the fracture ends were present to a greater extent in the high-virulent cohort and barely detectable in low-virulent infected mice. In both cohorts, no bone healing was observed after 4 days. On day 14, bone healing at the fracture site was visible in low-virulent infected animals, whereas callus formation was observed in only one animal from the high-virulent infected cohort. Furthermore, osteonecrosis and osteolysis were increased in high-virulent infected animals. Regarding serum cytokines, innate immune markers were elevated in both groups at day 4. By day 14, a more pronounced proinflammatory response indicated by increased serum cytokine levels of IFN-γ, IL-1β, and IL-6 was observed in high-virulent infected animals. Conclusions. The present study demonstrated distinct bacteriological and histopathological differences between two different virulent S. aureus strains previously shown to have different courses in human patients. While host physiology is often considered to have a major impact on the course of FRI, this study highlights the critical influence of the invading pathogen and its virulence characteristics

Aims. Bone demonstrates good healing capacity, with a variety of strategies being utilized to enhance this healing. One potential strategy that has been suggested is the use of stem cells to accelerate healing. Methods. The following databases were searched: MEDLINE, CENTRAL, EMBASE, Cochrane Database of Systematic Reviews, WHO-ICTRP, ClinicalTrials.gov, as well as reference checking of included studies. The inclusion criteria for the study were: population (any adults who have sustained a fracture, not including those with pre-existing bone defects); intervention (use of stem cells from any source in the fracture site by any mechanism); and control (fracture healing without the use of stem cells). Studies without a comparator were also included. The outcome was any reported outcomes. The study design was randomized controlled trials, non-randomized or observational studies, and case series. Results. In all, 94 eligible studies were identified. The clinical and methodological aspects of the studies were too heterogeneous for a meta-analysis to be undertaken. A narrative synthesis examined study characteristics, stem cell methods (source, aspiration, concentration, and application) and outcomes. Conclusion. Insufficient high-quality evidence is available to determine the efficacy of stem cells for fracture healing. The studies were heterogeneous in population, methods, and outcomes. Work to address these issues and establish standards for future research should be undertaken. Cite this article: Bone Joint Open 2020;1-10:628–638

Aim. Open fractures with bone defects and skin lesions carry a high risk of infection potentially leading to prolonged hospitalization and complication requiring revision procedures. Treatment options for diaphyseal fractures with soft tissue lesions are one- or two-stage approaches using external fixation or intramedullary nailing. We describe a surgical technique combining intramedullary nailing with an antibiotic-eluting biphasic bone substitute (BBS) applied both at the fracture site, for dead-space management and infection prevention, and on the nail surface for the prophylaxis of implant-related infection. Method. Adult patients with an increased risk of bony infection (severe soft tissue damage and open fractures of Gustilo-Anderson grades I and II) were treated with debridement followed by application on the intramedullary nail surface, in the canal and at the fracture site of a BBS with prolonged elution (to 28 days) of either gentamicin or vancomycin. All patients also received systemic antibiotic prophylaxis following surgery. Data on infections and other adverse events were collected throughout the follow-up period. Bone union was determined by radiographic assessment of 4 cortices in radiographs obtained 1 year after surgery. Results. In this prospective, non-randomized case series a total of 6 patients were treated: 4 tibia (2 male, 2 female), 1 femur (female) and 1 humerus (male). The mean age of the patients was 28 years (range 18–51 years). Two patients had a history of smoking and 1 patient had a history of diabetes. Minimal Follow up was 12 months (range: 12 – 30 months). One to two weeks postoperatively, partial load bearing (20 kg) was allowed with free mobility of joints. Bone samples from the fracture site following debridement showed the presence of bacteria in 2 cases. No infections were observed during follow-up. Radiographs showed that the bone substitute was resorbed and also a gradual bony union of the fractures. All patients had good clinical outcomes. Conclusions. The addition of a BBS which elutes antibiotic locally in the dead-space of exposed fractures and at the implant surface prevents bacterial colonization and biofilm formation. The injectable composite we used enhances safety in higher risk patients, is easy to use in combination with intramedullary nailing and offers the opportunity for a one-stage procedure. Local administration of antibiotics at the fracture site provides an additional tool to manage difficult-to-treat complex fractures and implant-related infections. Larger studies are needed to confirm these results. *CERAMENT G or V, BONESUPPORT AB

Introduction. Non-unions often arise because of high strain environments at fracture sites. Revision fixation, bone grafting and biologic treatments to treat long bone fracture non-union can be expensive and invasive. Percutaneous strain reduction screws (PSRS) can be inserted as a day-case surgical procedure to supplement primary fixation at a fraction of the cost of traditional treatments. Screw insertion perpendicular to the plane of a non-union can resist shear forces and achieve union by modifying the strain environment. A multi-centre retrospective study was undertaken to confirm the results of the initial published case series, ascertain whether this technique can be adopted outside of the developing institution and assess the financial impact of this technique. Materials and Methods. Retrospective analysis was performed for all PSRS cases used to treat un-united long bone fractures in four level 1 trauma centres from 2016 to 2020. All patients were followed up until union was achieved or further management was required. Demographic data was collected on patients, as were data about their injuries, initial management and timings of all treatments received. A comparative cost analysis was performed comparing patients treated with PSRS and with traditional non-union surgery methods. Results. 51 patients were treated with the PSRS technique. 45 (88%) patients achieved union at a median time of 5.2 months (range 1.0 – 24.7). Comparable results were seen between the developing institution and independent units. No patients experienced adverse events beyond failure to achieve union. PSRS appears to offer savings of between £2,957 to £11,231 per case compared with traditional methods of non-union surgery. Conclusions. PSRS is a safe, cost-effective treatment for long bone non-union. The promising results of the initial case series have now been replicated outside of the developing institution

Introduction. Management of open fractures is challenging and requires a multidisciplinary team approach. Gustilo Anderson Type IIIB fractures reportedly have a higher infection rate (up to 52%) and up to 16% amputation rate. This study aims to evaluate outcomes of using Adjuvant Local Antibiotic Hydroxyapatite Bio-Composite in management of Open Gustilo-Anderson IIIB fractures. Materials and Methods. We reviewed a prospective data of 80 patients who presented with Gustilo Anderson Type IIIB Open Fracture to a single ortho-plastic centre. Only patients who were managed with single-stage “Fix and Flap” along with intra-operative Adjuvant Local Antibiotic Bio-Composite were included. Results. Mean follow-up time was 22 months. The mean time from injury until definitive surgery was 7.73 days (1–30 days). Primary union achieved in 88.3% within 32 weeks on average. The delayed union reported in 7.8% of patients, for the bone healing stimulated by injecting the fracture site with Autologous Bone Marrow Aspirate Concentrate. Subsequent follow-up showed signs of successful fracture healing at 60 weeks post-injury. Three patients (3.9%) had non-union. Limb salvage rate was 96.25%, and only 1.25% deep infection rate. Conclusions. Our results highlight that low infection rates, high limb salvage rates and high union rates can be achieved in these complex injuries with a combined OrthoPlastic approach, MDT input, meticulous technique and the use of adjuvant local antibiotic bio-composite. Delay in definitive surgery, gentamicin resistance and smoking were not associated with any increased deep infection or non-union in our series. At 22 months of follow-up, deep infection rate was 1.25%, limbs salvage rate was 96.25%, fracture union rate was 96.1%, and reoperation rate 18.75%

Introduction. IM (Intra Medullary) nail fixation is the standard treatment for diaphyseal femur fractures and also for certain types of proximal and distal femur fractures. Despite the advances in the tribology for the same, cases of failed IM nail fixation continue to be encountered routinely in clinical practice. Common causes are poor alignment or reduction, insufficient fixation and eventual implant fatigue and failure. This study was devised to study such patients presenting to our practice and develop a predictive model for eventual failure. Materials and Methods. 57 patients who presented with failure of IM nail fixation (± infection) between Jan 2011 – Jun 2020 were included in the study and hospital records and imaging reviewed. Those fixed with any other kinds of metalwork were excluded. Classification for failure of IM nails – Type 1: Failure with loss of contact of lag screw threads in the head due to backing out and then rotational instability, Type 2A: Failure of the nail at the nail and lag screw junction, Type 2B: Failure of the screws at the nail lag screw junction, Type 3: Loosening at the distal locking sites with or without infection. X-rays reviewed and causes/site of failure noted. Results. Total patients - 57. Demography - Average age - 58.9 years, 22 Males and 35 females. Eleven patients were noted to have an infection at the fracture site that needed oral or IV antibiotics.16 patients - at least 1 cerclage wire for fracture reduction and fixation + IM Nail. Subtrochanteric fractures (42/57) were the most common to fail. In those fractures with postero-medial comminution, locking of the lag screw in position thus preventing backout can prevent failure. In type 2 failures, preventing varus fixation by early open reduction and temporary fixation with plates and screws can achieve improved results. Those with type 3 failures with periosteal reaction should be considered to be infected until proven otherwise. Conclusions. This classification for failure of IM nails in the femur can be used as a predictive model for failures and allow early recognition and intervention to tackle them

Tibial shaft fractures co-existing with osteoarthritis can increase the challenges for the orthopedic surgeon. The novel Londhe-Shah technique manages both the problems using one-stage total knee arthroplasty with a long stemmed tibial component which has a good diaphyseal fit. Three osteoarthritis patients with fractures of tibial shaft were treated with this technique and were followed up at 6-weeks, 12-weeks and 1-year (figure 1–3). A complete union of the fractured segment was achieved at follow-up without any adverse events such as infection, damage to the implant, and soft-tissue injury during and after surgery. The American Knee Society Score (AKSS) improved and WOMAC pain and stiffness scores reduced at follow-ups suggesting excellent improvement in functionality and patient satisfaction. One-stage TKR with a long-stem extension of the tibial component to bypass the fracture site mends and stabilises the fracture along with the adverse biomechanics at the fracture site while also correcting the arthritis. The single stage procedure allows early ambulation in six weeks. For any figures or tables, please contact the authors directly

Treat to target is the use of a physiologic marker as a monitor of effectiveness or compliance to an intervention. A recent example has been the progressive use of CTX-1 (Marker of osteoclastic activity) as a surrogate of bone resorptive activity in osteoporosis treatment. CTX-1 levels were demonstrated to be inversely related to drug efficacy in the suppression of bone resorption. As far as fragility fractures are concerned, no reference value of CTX-1 for any index fracture sites was found in the literature. In order to prevent subsequent fractures, efforts to better manage this chronic disease are to be explored. The main objective of this study was to compare and validate the use of serum CTX-1 to the perceived compliance to treatment. Five hundred and forty three patients (men and women) 40 years of age or older who had been treated for a fragility fracture were enrolled. The purpose of this study was to correlate the measurement of CTX-1 with the perceived compliance to treatment of patients at the time of fracture and at six, 12 and 18 months after initiation of treatment. Our secondary objectives were to evaluate two different CTX-1 suppression target levels (CTX-1< 0.3 ng/mL and CTX-1<0.2 ng/mL), to determine CTX-1 values according to fracture sites, and to explore the profile of patients with subsequent fractures. Considering index fractures, compliant patients under treatment at baseline had lower CTX-1 levels than non-compliant patients (p=0.052). Patients who were compliant to treatment at six, 12 and 18 months also had lower CTX-1 levels than non-compliant patients (p=0.000). When index fractures were divided into fracture sites, regardless of CTX-1 suppression target level (i.e. CTX-1< 0.3 or 0.2 ng/mL), significant CTX-1 suppression was observed in non-hip and non-vertebral (NHNV) fractures at six, 12 and 18 months (p0.05). No clinically relevant difference was observed between the profile of patients with and without subsequent fractures. The correlation between serum CTX-1 at the time of fracture and at six, 12, 18 months and the perceived compliance to treatment was validated for NHNV fractures supporting the concept of the available treatments and their effects on bone remodeling for this type of fracture. The correlation was not validated for hip neither for vertebral fracture. There was no correlation between CTX-1 levels and subsequent fracture risk

Bone fracture healing is regulated by a series of complex physicochemical and biochemical processes. One of these processes is bone mineralisation, which is vital for normal bone development, its biomechanical competence and fracture healing. Phosphatase, orphan 1 (PHOSPHO1), a bone-specific phosphatase, has been shown to be involved in the mineralisation of the extracellular matrix in bone. It can hydrolyse phosphoethanolamine and phosphocholine to generate inorganic phosphate, which is crucial for bone mineralisation. Phospho1−/− mice show hypomineralised bone and spontaneous fractures. All these data led to the hypothesis that PHOSPHO1 is essential for bone mineralisation and its structural integrity. However, no study to our knowledge has shown the effects of PHOSPHO1 on bone fracture healing. In this study, we examined how PHOSPHO1-deficiency might affect the healing and quality of the fractured bones in Phospho1−/− mice. We performed rodded immobilised fracture surgery on the right tibia of control wild type (WT) and Phospho1−/− mice (n=16 for each group) at eight weeks of age. Bone was left to heal for four weeks and then the mice were euthanised and their tibias were analysed using Faxitron X-ray analyses, microCT, histology and histomorphometry and three-point bending test. Our microCT and X-ray analyses revealed that the appearance of the callus and several static parameters of bone remodeling at the fracture sites were markedly different in WT and Phospho1−/− mice. We observed a significant increase of BS/BV, BS/TV and trabecular number and decrease in trabecular thickness and separation in Phospho1−/− callus in comparison to the WT callus. These observations were further confirmed by histomorphometry. The increased bone mass at the fracture sites of Phospho1−/− mice appears to be caused by increased bone formation as there is a significant increase of osteoblast number, while osteoclast numbers remained unchanged. There was a marked increase of osteoid volume over bone volume (OV/BV) in the Phospho−/− callus. Interestingly, the amount of osteoid was markedly higher at the fracture sites than that of normal trabecular bones. The three-point bending test showed that Phospho 1 −/− fractured bone had more of an elastic characteristics than the WT bone as they underwent more of a plastic deformity before the breakage point compare to the WT. Our work suggests that PHOSPHO1 plays an integral role during bone fracture repair. PHOSPHO1 can be an interesting target to improve the fracture healing process

For the management of displaced patellar fractures, surgical fixation using cannulated screws along with anterior tension band wiring is getting popular. Clinical and biomechanical studies have reported that using cannulated screws and a wire instead of the modified tension band with Kirschner wires improves the stability of fractured patellae. However, the biomechanical effect of screw proximity on the fixed construction remains unclear. The aim of this study was to evaluate the mechanical behaviors of the fractured patella fixed with two cannulated screws and tension band at different depths of the patella using finite element method. A patella model with simple transverse fracture [AO 34-C1] was developed; the surgical fixation consisted of two 4.0-mm parallel partial-threaded cannulated screws with a figure-of-eight anterior tension band wiring using a 1.25-mm stainless steel cable. Two different locations, including the screws 5-mm and 10-mm away from the leading edge of the patella, were used. A tension force of 850 N was applied on the patellar apexes at two loading angles (45° and 0° [parallel] to the long axis) to simulate different loading conditions while knee ambulation. The proximal side (base) of the patella was fixed, and the inferior articular surface was defined as a compression-only support in ANSYS to simulate the support from distal femur condyles. Compression-only support enables the articular surfaces of the present patella to only bear compression and no tension forces. Under different loading conditions, the fixed fractured patella yielded higher stability during 0° loading of tension force than during 45° loading. When the screws were parallel placed at the depth of 5 mm away from the patellar surface, the deformation of patellar fragment and maximum gap opening at the fracture site were smaller than those obtained by screws placed at the depth of 10 mm away from the patellar surface. Compared to the superficial screw placement, the deeper placement (10 mm) increased the maximum gap opening at the fracture site by 1.56 times under 45° loading, and 1.58 times under 0° loading. The load on the tension band wire of the 10-mm screw placement was 3.12 times (from 230 to 717 N) higher than that of the 5-mm placement. Under the wire, the contact pressure on the patellar surface was higher with the 10-mm screw placement than the 5-mm screw placement. The peak bone contact pressures with the 10-mm placement were 7.7 times (99.5 to 764 MPa) higher. This is the first numerical study to examine the biomechanical effects of different screw locations on the fixation of a fractured patella using screws and tension band. Based on a higher stability and lower cable tension obtained by the superficial screws placement, the authors recommended the superficial screw placement (5 mm below the leading edge of the patella) rather than the deep screws while fixing the transverse patellar fracture with cannulated screws and cable

Treatment of segmental bone defects remains a major clinical problem, and innovative strategies are often necessary to successfully reconstruct large volumes of bone. When fractures occur, the resulting hematoma serves as a reservoir for growth factors and a space for cell infiltration, both crucial to the initiation of bone healing. Our previous studies have demonstrated very clear ultrastructural differences between fracture hematomas formed in normally healing fractures and those formed in segmental bone defects. However, there is little information available regarding potential differences in the underlying gene expression between hematomas formed in normal fractures, which usually heal by themselves, and segmental bone defects, which do not. Therefore, the aim of this study was to identify differences in gene expression within hematomas collected from 0.5 mm (normal fracture) and 5 mm (segmental bone defect) fracture sites during the earliest stages of bone healing. Osteotomies of 0.5 and 5 mm in the femur of Fisher 344 rats were stabilized with external fixators (RISystem AG). After 3 days the rats were sacrificed, and the fracture hematomas were collected for RNA-sequencing. Ingenuity pathway analysis (IPA) was used to identify upstream regulators and biological functions that were significantly enriched with differentially expressed genes from the RNA-sequencing analysis. Animal procedures were conducted following the IACUC protocol of the UT Health Science Center San Antonio. Key upstream regulators of bone formation were less active (e.g. TGFB1, FGF2, SMAD3) or even inhibited (e.g. WNT3A, RUNX2, BMP2) in non-healing defects when compared to normally healing fractures. Many upstream regulators that were uniquely enriched in healing defects were molecules recently discovered to have osteogenic effects during fracture healing (e.g. GLI1, EZH2). Upstream regulators uniquely enriched in non-healing defects were mainly involved in an abnormal modulation of hematopoiesis, revealing evidence of impaired maturation of functional macrophages and cytokines (e.g. IL3, CEBPE), both essential for successful bone healing. In addition, the enrichment pattern suggested a dysregulation of megakaryopoiesis (e.g. MRTFA, MRTFB, GATA2), which directly affects platelet production, and therefore fracture hematoma formation. Remarkably, the organization of the ECM was the most significantly enriched biological function in the normally healing fractures, and implies that the defect size directly affected the structural properties within the fracture hematoma. Conversely, genes encoding important ECM components (e.g. BGN, various collagens, IBSP, TNC), cell adhesion molecules, MMPs (MMP2), and TIMPs were all significantly downregulated in non-healing defects. Our most recent findings reveal new important key molecules that regulate defect size-dependent fracture healing. Combined with our previous results, which identified structural differences in fracture hematomas from both types of defects, current findings indicate that differential expression of genes is dictated by the structural properties of the hematomas formed during early fracture healing. Consequently, creating a bioscaffold that mimics the structure of normal fracture hematomas could be the first step towards developing new orthoregenerative treatment strategies that potentiate healing of large bone defects and non-healing fractures

Bone regeneration includes a well-orchestrated series of biological events of bone induction and conduction. Among them, the Wnt/β-catenin signaling pathway is critical for bone regeneration. Being involved in several developmental processes, Wnt/β-catenin signaling must be safely targeted. There are currently only few specific therapeutic agents which are FDA-approved and already entered clinical trials. A published work has shown that Tideglusib, a selective and irreversible small molecule non-ATP-competitive glycogen synthase kinase 3-β(GSK-3β) inhibitor currently in trial for Alzheimer's patients, can promote tooth growth and repair cavities. [1]Despite some differences, they are some similarities between bone and tooth formation and we hypothesise that this new drug could represent a new avenue to stimulate bone healing. In this work, we locally delivered Tideglusib (GSK3β inhibitor) in the repair of femoral cortical window defects and investigated bone regeneration. A biodegradable FDA-approved collagen sponge was soaked in GSK-3βinhibitor solution or vehicle only (DMSO) and was implanted in 1 × 2 mm unicortical defects created in femora of 35 adult wild-type male mice. Bone defect repair on control and experimental (GSK-3βinhibitor) groups was assessed after 1 week (n=22), 2 weeks (n=24) and 4 weeks (n=24) with microCT and histological analysis foralkaline phosphatase (ALP, osteoblast activity), tartrate resistant acid phosphatase (TRAP, osteoclasts), and immunohistochemistry to confirm the activation of the Wnt/β-catenin pathway. Our results showed that Tideglusib significantly enhanced cortical bone bridging (20.6 ±2.3) when compared with the control (12.7 ±1.9, p=0.001). Activity of GSK-3β was effectively downregulated at day 7 and 14 resulting in a higher accumulation of active β-catenin at day 14 in experimental group (2.5±0.3) compared to the control (1.1±0.2, p=0.03). Furthermore, the onset of ALP activity appears earlier in the experimental group (day 14, 1.79±0.28), a level of activity never reached at any end-point by the control defects. At 4 weeks treatment, we observed a significant drop in ALP in the experimental group (0.47±0.05) compared to the control (1.01±0.19, p=0.02) and a decrease in osteoclast (experimental=1.32±0.36, control=2.23±0.67, p=0.04). Local downregulation of GSK-3β by tideglusib during bone defect repair resulted in significant increase in amount of new bone formation. The early upregulation of osteoblast activity is one explanation of bone healing augmentation. This is likely the effect of upregulation of β-catenin following pharmaceutical inhibition of GSK-3β since β-catenin activation is known to positively regulate osteoblasts, once committed to the osteoblast lineage. As a GSK-3β inhibitor, Tideglusib demonstrates a different mechanism of action compared with other GSK-3β antagonists as treatment was started immediately upon injury and did not interfere with precursor cells recruitment and commitment. This indicates that tideglusib could be used at the fracture site during the initial intraoperative internal fixation without the need for further surgery. This safe and FDA-approved drug could be used in prevention of non-union in patients presenting with high risk for fracture-healing complications

We investigated whether an alternative tension band wire technique will produce greater compression and less displacement at olecranon (elbow) fracture sites compared to a standard figure of eight tension band technique. Olecranon fractures are commonly treated with tension band wiring using stainless steel wire in a figure of eight configuration. However recently published studies have raised doubts over the validity of the tension band concept proving that the standard figure of eight configuration does not provide fracture compression when the elbow is flexed. We propose an alternative tension band technique where the figure of eight is applied in a modified configuration producing greater compression across the fracture. An artificial elbow joint was simulated using artificial forearm (ulna) and arm (humerus) bones. The design simulated the action of the muscles around the elbow joint to produce flexion and extension. There were two arms to this investigation. (1) Standard tension band wire configuration with stainless steel. (2) Modified tension band wire configuration with stainless steel. The simulated elbow was put through a range of movement and sensors measured the compression at the articular and non-articluar surfaces of the fracture. Measurements were taken for compression with different weights applied to challenge both the techniques of tension band wiring. Measurements from the non articular surface of the fracture demonstrated greater compression with alternative tension band technique. However it was not statistically significant (ANOVA). Compression at the articular surface of the fracture exhibited statistically significant (p<0.05) greater compression with the alternative technique. Neither technique produced greater compression during flexion of the simulated elbow. The alternative tension band wiring technique proved superior in providing greater compression over the fracture site

This edition of Cochrane Corner looks at some of the work published by the Cochrane Collaboration, covering interventions for treating distal femur fractures in adults; ultrasound and shockwave therapy for acute fractures in adults; and local corticosteroid injection versus placebo for carpal tunnel syndrome.