Introduction. The presence of pluripotent mesenchymal cells in the periosteum along with the growth factors produced or released following injury provides this tissue with an important role in bone healing. Utilising this property, vascularised periosteal flaps may increase the union rates in recalcitrant atrophic long bone non-union. The novel chimeric fibula-periosteal flap utilises the periosteum raised on an independent periosteal vessel, thus allowing the periosteum to be inset freely around the osteotomy site, improving bone biology. Materials & Methods. Ten patients, with established non-union, underwent fibula-periosteal chimeric flaps (2016–2022) at the Canniesburn Plastic Surgery Unit, UK. Preoperative CT angiography was performed to identify the periosteal branches. A case-control approach was used. Patients acted as their own controls, which obviated patient specific risks for non-union. One osteotomy site was covered by the chimeric periosteal flap and one without. In two patients both the osteotomies were covered using a long periosteal flap. Results. Union rate of 100% (11/11) was noted with periosteal flap osteotomies, versus those without flaps at 28.6% (2/7) (p = 0.0025). Time to union was also reduced in the periosteal flaps at 8.5 months versus 16.75 months in the control group (p = 0.023). Survival curves with a hazard ratio of 4.1, equating to a 4 times higher chance of union with periosteal flaps (log-rank p = 0.0016) was observed. Conclusions. The chimeric fibula-periosteal flap provides an option for atrophic recalcitrant non-unions where use of vascularised fibula graft alone may not provide an adequate biological environment for consolidation

Impaired bone healing biology secondary to soft tissue deficits and chemotherapy contribute to non-union, fracture and infection following limb salvage surgery in Osteosarcoma patients. Approved bone healing augments such as recombinant human bone morphogenetic protein-2 (rhBMP-2) have great potential to mitigate these complications. rhBMP-2 use in sarcoma surgery is limited, however, due to concerns of pro-oncogenic signalling within the tumour resection bed. To the contrary, recent pre-clinical studies demonstrate that BMP-2 may induce Osteosarcoma differentiation and limit tumour growth. Further pre-clinical studies evaluating the oncologic influences of BMP-2 in Osteosarcoma are needed. The purpose of this study is to evaluate how BMP-2 signalling affects Osteosarcoma cell proliferation and metastasis in an active tumour bed. Two Osteosarcoma cell lines (143b and SaOS-2) were assessed for proliferative capacity and invasion. 143b and SaOS-2 cells were engineered to upregulate BMP-2. In vitro proliferation was assessed using a cell viability assay, motility was assessed with a scratch wound healing assay, and degree of osteoblastic differentiation was assessed using qRT-PCR of Osteoblastic markers (CTGF, ALP, Runx-2 and Osx). For in vivo evaluation, Osteosarcoma cells were injected into the intramedullary proximal tibia of immunocompromised (NOD-SCID) mice and local tumour growth and metastases were assessed using weekly bioluminescence imaging (BLI) and tumour volume measurements for 4–6 weeks. At the experimental end point we assessed radiographic tumour burden using ex-vivo micro-CT, as well as tibial and pulmonary gross and histologic pathology. SaOS-2 was more differentiated than 143b, with increased expression of Runx-2 (p = 0.009), Osx (p = 0.004) and ALP (p = 0.035). BMP-2 upregulation did not stimulate an osteoblast differentiation response in 143b, but stimulated an increase in Osx expression in SaOS-2 (p = 0.002). BMP-2 upregulation in 143b cells resulted in increased proliferation in vitro (p = 0.014), faster in vitro wound healing (p = 0.03), significantly increased tumour volume (p = 0.001) with enhanced osteolysis detected on micro-CT, but did not affect rates of lung metastasis (67% vs. 71%, BMP-2 vs. Control). BMP-2 over-expression in SaOS-2 cells reduced in vitro proliferation when grown in partial osteogenic-differentiation media (p < 0.001), had no effect on in vitro wound healing (p = 0.28), reduced in vivo SaOS-2 tumour burden at 6 weeks (photon counts, p < 0.0001), decreased tumour-associated matrix deposition as assessed by trabecular thickness (p = 0.02), and did not affect rates of lung metastasis (0% vs. 0%). Our results indicate BMP-2 signalling incites a proliferative effect on a poorly differentiated Osteosarcoma cell line (143b), but conditionally reduces proliferative capacity and induces a partial differentiation response in a moderately-differentiated Osteosarcoma cell line (SaOS-2). This dichotomous effect may be due to the inherent ability for Osteosarcoma cells to undergo BMP-2 mediated terminal differentiation. Importantly, these results do not support the clinical application of BMP-2 in Osteosarcoma limb salvage surgery due to the potential for stimulating growth of poorly differentiated Osteosarcoma cells within the tumour bed. Additional studies assessing the effects of BMP-2 in an immune-competent mouse model are ongoing

Impaired bone healing biology secondary to soft tissue deficits and chemotherapy contribute to non-union, fracture and infection following limb salvage surgery in Osteosarcoma patients. Approved bone healing augments such as recombinant human bone morphogenetic protein-2 (rhBMP-2) have great potential to mitigate these complications. rhBMP-2 use in sarcoma surgery is limited, however, due to concerns of pro-oncogenic signalling within the tumour resection bed. To the contrary, recent pre-clinical studies demonstrate that BMP-2 may induce Osteosarcoma differentiation and limit tumour growth. Further pre-clinical studies evaluating the oncologic influences of BMP-2 in Osteosarcoma are needed. The purpose of this study is to evaluate how BMP-2 signalling affects Osteosarcoma cell proliferation and metastasis in an active tumour bed. Two Osteosarcoma cell lines (143b and SaOS-2) were assessed for proliferative capacity and invasion. 143b and SaOS-2 cells were engineered to upregulate BMP-2. In vitro proliferation was assessed using a cell viability assay, motility was assessed with a scratch wound healing assay, and degree of osteoblastic differentiation was assessed using qRT-PCR of Osteoblastic markers (CTGF, ALP, Runx-2 and Osx). For in vivo evaluation, Osteosarcoma cells were injected into the intramedullary proximal tibia of immunocompromised (NOD-SCID) mice and local tumour growth and metastases were assessed using weekly bioluminescence imaging and tumour volume measurements for 4–6 weeks. At the experimental end point we assessed radiographic tumour burden using ex-vivo micro-CT, as well as tibial and pulmonary gross and histologic pathology. SaOS-2 was more differentiated than 143b, with significantly increased expression of the Osteoblast markers Osx (p = 0.004) and ALP (p = 0.035). BMP-2 upregulation did not stimulate an osteoblast differentiation response in 143b, but stimulated an increase in Osx expression in SaOS-2 (p = 0.002). BMP-2 upregulation in 143b cells resulted in increased proliferation in vitro (p = 0.014), faster in vitro wound healing (p = 0.03), significantly increased tumour volume (p = 0.001) with enhanced osteolysis detected on micro-CT, but did not affect rates of lung metastasis (67% vs. 71%, BMP-2 vs. Control). BMP-2 over-expression in SaOS-2 cells reduced in vitro proliferation when grown in osteogenic-differentiation media (p < 0.001), had no effect on in vitro wound healing (p = 0.28), reduced in vivo SaOS-2 tumour burden at 6 weeks (photon counts, p < 0.0001), decreased tumour-associated matrix deposition as assessed by trabecular thickness (p = 0.02), but did not affect rates of lung metastasis (0% vs. 0%). Our results indicate BMP-2 signalling incites a proliferative effect on a poorly differentiated Osteosarcoma cell line (143b), but conditionally reduces proliferative capacity and induces a partial differentiation response in a moderately-differentiated Osteosarcoma cell line (SaOS-2). This dichotomous effect may be due to the inherent ability for Osteosarcoma cells to undergo BMP-2 mediated terminal differentiation. Importantly, these results do not support the clinical application of BMP-2 in Osteosarcoma limb salvage surgery due to the potential for stimulating growth of poorly differentiated Osteosarcoma cells within the tumour bed. Additional studies assessing the effects of BMP-2 in an immune-competent mouse model are ongoing

Massive uncontained glenoid defects are a difficult surgical problem requiring reconstruction in the setting of either primary or revision total shoulder arthroplasty. Our aim is to present a new one-stage technique that has been developed in our institution for glenoid reconstruction in the setting of massive uncontained glenoid bone loss. We utilise a modified delto-pectoral approach to perform our dual biology allograft autograft glenoid reconstruction. The native glenoid and proximal femoral allograft are prepared and shaped to create a precisely matched contact surface, which permits axial compression to secure fixation. The surface of the glenoid is lateralised to at least the level of the coracoid. The central cancellous femoral allograft is removed and impaction autografting is performed prior to implantation of a glenoid base plate with 25-mm long centre peg. Two screws are inserted into the best quality native scapular bone available to ensure compression. A reverse shoulder arthroplasty is implanted. We have performed our dual-biology reconstruction of the glenoid in combination with reverse total shoulder arthroplasty in 8 patients to date. The technique has been performed in the setting of massive uncontained glenoid defects without prostheses as well as in revisions from failed hemiarthroplasties and total shoulder arthroplasties. Our post-operative follow-up is now up to 32 months. CT scanning as early as 6 months demonstrates incorporation of the graft. There has been no evidence of loosening. None of our cases have been complicated by infection or peri-prosthetic fracture and there have been no dislocations. One patient sustained an acromial stress fracture at 9 months post-operatively after lifting a 100-pound gas cylinder. This was diagnosed on bone scan, had no impact on the construct and was managed in a sling for comfort. Another patient has developed Nerot grade I notching which substantially in all patients, with an average improvement of 6.6 on a 10-point scale. Our dual biology allograft-autograft reconstruction is a useful and elegant technique in the setting of massive uncontained defects of the glenoid, which permits the implantation of a reverse total shoulder arthroplasty. We believe this technique to be reproducible and uses materials that are both readily available and familiar

Advances in cancer therapy have prolonged patient survival even in the presence of disseminated disease and an increasing number of cancer patients are living with metastatic bone disease (MBD). The proximal femur is the most common long bone involved in MBD and pathologic fractures of the femur are associated with significant morbidity, mortality and loss of quality of life (QoL). Successful prophylactic surgery for an impending fracture of the proximal femur has been shown in multiple cohort studies to result in longer survival, preserved mobility, lower transfusion rates and shorter post-operative hospital stays. However, there is currently no optimal method to predict a pathologic fracture. The most well-known tool is Mirel's criteria, established in 1989 and is limited from guiding clinical practice due to poor specificity and sensitivity. The ideal clinical decision support tool will be of the highest sensitivity and specificity, non-invasive, generalizable to all patients, and not a burden on hospital resources or the patient's time. Our research uses novel machine learning techniques to develop a model to fill this considerable gap in the treatment pathway of MBD of the femur. The goal of our study is to train a convolutional neural network (CNN) to predict fracture risk when metastatic bone disease is present in the proximal femur. Our fracture risk prediction tool was developed by analysis of prospectively collected data of consecutive MBD patients presenting from 2009–2016. Patients with primary bone tumors, pathologic fractures at initial presentation, and hematologic malignancies were excluded. A total of 546 patients comprising 114 pathologic fractures were included. Every patient had at least one Anterior-Posterior X-ray and clinical data including patient demographics, Mirel's criteria, tumor biology, all previous radiation and chemotherapy received, multiple pain and function scores, medications and time to fracture or time to death. We have trained a convolutional neural network (CNN) with AP X-ray images of 546 patients with metastatic bone disease of the proximal femur. The digital X-ray data is converted into a matrix representing the color information at each pixel. Our CNN contains five convolutional layers, a fully connected layers of 512 units and a final output layer. As the information passes through successive levels of the network, higher level features are abstracted from the data. The model converges on two fully connected deep neural network layers that output the risk of fracture. This prediction is compared to the true outcome, and any errors are back-propagated through the network to accordingly adjust the weights between connections, until overall prediction accuracy is optimized. Methods to improve learning included using stochastic gradient descent with a learning rate of 0.01 and a momentum rate of 0.9. We used average classification accuracy and the average F1 score across five test sets to measure model performance. We compute F1 = 2 x (precision x recall)/(precision + recall). F1 is a measure of a model's accuracy in binary classification, in our case, whether a lesion would result in pathologic fracture or not. Our model achieved 88.2% accuracy in predicting fracture risk across five-fold cross validation testing. The F1 statistic is 0.87. This is the first reported application of convolutional neural networks, a machine learning algorithm, to this important Orthopaedic problem. Our neural network model was able to achieve reasonable accuracy in classifying fracture risk of metastatic proximal femur lesions from analysis of X-rays and clinical information. Our future work will aim to externally validate this algorithm on an international cohort

Advances in cancer therapy have prolonged cancer patient survival even in the presence of disseminated disease and an increasing number of cancer patients are living with metastatic bone disease (MBD). The proximal femur is the most common long bone involved in MBD and pathologic fractures of the femur are associated with significant morbidity, mortality and loss of quality of life (QoL). Successful prophylactic surgery for an impending fracture of the proximal femur has been shown in multiple cohort studies to result in patients more likely to walk after surgery, longer survival, lower transfusion rates and shorter post-operative hospital stays. However, there is currently no optimal method to predict a pathologic fracture. The most well-known tool is Mirel's criteria, established in 1989 and is limited from guiding clinical practice due to poor specificity and sensitivity. The goal of our study is to train a convolutional neural network (CNN) to predict fracture risk when metastatic bone disease is present in the proximal femur. Our fracture risk prediction tool was developed by analysis of prospectively collected data for MBD patients (2009–2016) in order to determine which features are most commonly associated with fracture. Patients with primary bone tumors, pathologic fractures at initial presentation, and hematologic malignancies were excluded. A total of 1146 patients comprising 224 pathologic fractures were included. Every patient had at least one Anterior-Posterior X-ray. The clinical data includes patient demographics, tumor biology, all previous radiation and chemotherapy received, multiple pain and function scores, medications and time to fracture or time to death. Each of Mirel's criteria has been further subdivided and recorded for each lesion. We have trained a convolutional neural network (CNN) with X-ray images of 1146 patients with metastatic bone disease of the proximal femur. The digital X-ray data is converted into a matrix representing the color information at each pixel. Our CNN contains five convolutional layers, a fully connected layers of 512 units and a final output layer. As the information passes through successive levels of the network, higher level features are abstracted from the data. This model converges on two fully connected deep neural network layers that output the fracture risk. This prediction is compared to the true outcome, and any errors are back-propagated through the network to accordingly adjust the weights between connections. Methods to improve learning included using stochastic gradient descent with a learning rate of 0.01 and a momentum rate of 0.9. We used average classification accuracy and the average F1 score across test sets to measure model performance. We compute F1 = 2 x (precision x recall)/(precision + recall). F1 is a measure of a test's accuracy in binary classification, in our case, whether a lesion would result in pathologic fracture or not. Five-fold cross validation testing of our fully trained model revealed accurate classification for 88.2% of patients with metastatic bone disease of the proximal femur. The F1 statistic is 0.87. This represents a 24% error reduction from using Mirel's criteria alone to classify the risk of fracture in this cohort. This is the first reported application of convolutional neural networks, a machine learning algorithm, to an important Orthopaedic problem. Our neural network model was able to achieve impressive accuracy in classifying fracture risk of metastatic proximal femur lesions from analysis of X-rays and clinical information. Our future work will aim to validate this algorithm on an external cohort

To elucidate the molecular biology of fracture healing, murine models are preferred. We performed a study with the first internal fixation system that allows studying murine fracture healing in a controlled mechanical environment, to characterise the timing of the fracture healing cascade with this model, based on a histological evaluation. Femoral osteotomies were performed in 68 male C57BL/six mice and stabilised with locking internal fixation plates in either stiff, or defined, flexible configurations. Healing progression was studied at 10 time points between 3 and 42 days post- surgery. After surgery, mice were radiographed to confirm the correct implant positioning. After sacrifice, the extracted femora were processed for decalcified histology. Thin sections were taken as serial transverse sections and stained for subsequent histomorphometric analysis and three-dimensional reconstruction of the different fracture callus tissues. The surgery was successful in 62 animals. Only six6 (8.8%) animals had to be sacrificed due to complications during surgery. The post-operative radiographs demonstrated a high reproducibility of implant positioning and no implant failure or screw loosening occurred during the experimental period. The improved consistency in surgical technique leading to more uniform results represents a key advantage of this system over other mouse fracture healing models. As such, it may allow a reduction in the sample size needed in future murine fracture healing studies. The histological evaluation confirmed the lack of a periosteal callus, and exclusively endosteal, intramembraneous bone formation in the bones stabilised with the stiff implants. The bones that were stabilised with the more flexible internal fixation plates showed additional endochondral ossification with extensive, highly asymmetrical, periosteal callus formation. Our results demonstrate that this murine fracture model leads to different healing patterns depending on the flexibility of the chosen plate system. This allows researchers to investigate the molecular biology of fracture healing in different ossification modes by selection of the appropriate fixation

Pelvic discontinuity is defined as a separation of the ilium superiorly from the ischiopubic segment inferiorly. In 2018, the main management options include the following: 1) hemispheric acetabular component with posterior column plating, 2) cup-cage construct, 3) pelvic distraction, and 4) custom triflange construct. A hemispheric acetabular component with posterior column plating is a good option for acute pelvic discontinuities. However, healing potential is dependent on host's biology and characteristic of the discontinuity. The plate should include 3 screws above and 3 screws below the discontinuity with compression in between. In addition, the hemispherical acetabular component should have at least 50% host bone contact with 3–4 screws superior and 2–3 screws inferior to the discontinuity. On the other hand, a cup-cage construct can be used in any pelvic discontinuity. This includes a highly porous acetabular component placed on remaining host bone. Occasionally, highly porous metal augments are used to fill the remaining bone defects. A supplemental cage is placed over the acetabular component, spanning the discontinuity from the ilium to the ischium. A polyethylene liner is then cemented into place with antibiotic-loaded bone cement. Rarely, pelvic distraction may be needed. With this technique, pelvic stability is obtained via distraction of the discontinuity by elastic recoil of the pelvis and by fixing the superior hemipelvis and inferior hemipelvis to a highly porous metal cup or augment with screws, thereby unitizing the superior and inferior aspects of the pelvis. In essence, the cup acts as a segmental replacement of the acetabulum, with healing occurring to the cup or augment, resulting in a unitised hemipelvis. Frequently, the discontinuity itself does not achieve bony healing. Finally, custom triflange constructs are being utilised with increasing frequency. Triflange cups are custom-designed, porous and/or hydroxyapatite coated, titanium acetabular components with iliac, ischial, and pubic flanges. Rigid fixation promotes healing of the discontinuity and biologic fixation of the implant. It requires a CT scan, dedicated preoperative design, and fabrication costs

Prior to the 1970s, almost all bone sarcomas were treated by amputation. The first distal femoral resection and reconstruction was performed in 1973 by Dr Kenneth C Francis at the Memorial Sloan-Kettering Cancer Centre in New York. Since that time, limb-sparing surgery for primary sarcoma has become the mainstay of sarcoma surgery throughout the world. Initially, the use of mega-prostheses of increasing complexity, involving all the major long bones and both pelvic and shoulder girdles, was popularised. In the early 1980s, wide use of massive allograft reconstructions became widespread in both Europe and in multiple centres in the USA and UK. Since that time, increasing complexity in the design of prostheses has allowed for increasing functional reconstructions to occur, but the use of allograft has become less popular due to the development of late graft failures of patients survive past ten years. Fracture rates approaching 50% at 10 years are reported, and thus, other forms of reconstruction are being sought. Techniques of leg lengthening, and bone docking procedures to replace segmental bone loss to tumour are now employed, but the use of biological vascularised reconstructions are becoming more common as patient survivorship increases with children surviving their disease. The use of vascularised fibular graft, composite grafts and re-implantation of extra-corporeally irradiated bone segments are becoming more popular. The improvement in survivorship brought about the use of chemotherapy is producing a population of patients with at least a 65% ten year survivorship, and as many of these patients are children, limb salvage procedures have to survive for many decades. The use of growing prostheses for children have been available for some 25 years, first commencing in Stanmore, UK, with mechanical lengthening prostheses. Non-invasive electro-magnetic induction coil mechanisms are now available to produce leg lengthening, with out the need for open surgery. Whilst many of these techniques have great success, the area of soft tissue attachment to metallic prostheses has not been solved, and reattachment of muscles is of great importance, of course, for return of function. There are great problems in the shoulder joints where sacrifice of rotator cuff muscles is necessary in obtaining adequate disease clearance at the time of primary resection, and a stable shoulder construct, with good movement, has yet to emerge. Similar areas of great difficultly remain the peri-acetabular and sacro-iliac resections in the pelvis. Perhaps the real future of the art of limb salvage will be in the reconstruction of failed major joint replacements where there is great loss of bone stock, and already massive tumour prostheses are providing a salvage pathway for failed standard joint replacement. The final future for limb salvage, however, may not rest with increasing surgical complexity and innovation, but with the development of molecular biology and specific targeted treatments, according to the cytogenetics of a particular tumour. We are on the threshold of yet another quantum change in the approach to cancer management; just as chemotherapy brought a tremendous change in the 1970s, molecular biology is the frontier to make much of the current limb salvage surgery that is performed redundant

Aims

The purpose of this survey study was to examine the demographic and lifestyle factors of women currently in orthopaedic surgery.

Bone localization of tuberculosis mainly affects the thoracolumbar spine. The cervical spine is rare. Its diagnosis is often late which exposes to great instability and potentially serious complications. We reported the case of a patient with cervical spine tuberculosis with a rare localisation. A 10-years old boy with no medical history, showed torticolis and high temperature without neurological complication. In the physical examination, he had torticolis and pain in the third, forth and fifth cervical vertebra. The biology showed high CRP 200mg/l. The tomodensitometry of the cervical spine showed a collection of the third cervical spine. The patient took non specific Antibiotics for two months with no radiological improvement. When biopsy was performed, we find an inter apophysis (between C3 and C4) collection. The histological examination confirmed the diagnosis of apophysis tuberculosis. The cervical spine is a rare localisation of the tuberculosis. The apophysis localisation is a more uncommon localisation. The diagnosis is difficult. The histological examination is essential for the diagnosis. The management based on tuberculosis chemotherapy and immobilization started as soon as possible

Bone is capable of regeneration, and defects often heal spontaneously. However, cartilage, tendon, and ligament injuries usually result in replacement if the site by organized scar tissue, which is inferior to the native tissue. The osteogenic potential of mesenchymal stem cells (MSCs) has already been verified. MSCs hold great potential for the development of new treatment strategies for a host of orthopedic conditions. The multi-lineage potential and plasticity of MSCs allow them to be building blocks for a host of nonhematopoietic tissues, including bone. More recently, several groups have reported on the successful clinical application of tissue engineering strategies in the repair of bony defects in patients secondary to trauma and tumor resection. Advances in fabrication of biodegradable scaffolds that serve as beds for MSC implantation will hopefully lead to better biocompatibility and host tissue integration. Current strategies for bone tissue engineering include the use of osteoconductive matrix devices that promote bony ingrowth, and the delivery of osteoinductive growth factors, including bone morphogenetic protein (BMP) family, BMP-2 and BMP-7, to bony defect sites. Minimal toxicity has been observed in animal models involving genetically-manipulated stem cells transduced with retroviral and adenoviral vectors. Gene therapy using stem cells as delivery vehicles is a powerful weapon that can be used in a plethora of clinical situations that would benefit from the osteoinductive, proliferative, and angiogenic effects of growth factors. With better understanding of the biology of stem cells in the future and with enhancement of technologies that are capable to influence, modify, and culture these cells, a new field of regenerative skeletal medicine may emerge

Although there is strong evidence that bisphosphonates prevent certain types of osteoporotic fractures, there are concerns that they may be associated with rare atypical femoral fractures. 1480 patients of proximal femur and shaft fractures over a period of 2 years from Jan 2014 to Jan 2016 were retrospectively reviewed in Gloucestershire Hospitals NHS trust. Hospital trauma database was used.195 patients had fractures in subtrochancteric and femoral shaft area. 11 patients had atypical femur fractures as defined by American society for bone and mineral research (ASBMR) task force 2013, revised criteria. Ten were female, one was male. Patients were aged from 68 to 97. In 6 patients, fractures were in the shaft, 5 in subtrochancteric area and 4 patients out of these had bilateral fractures. 10 out of 11 patients were on bisphosphonates. 4 patients had delayed diagnosis. 5 out of 11 patients did not have contralateral femoral x-rays. Treatment, 9 patients had intramedullary nail, one blade plate, and one treated conservatively. One patient in the IM group, had bilateral nailing. Average follow up was 7.6 months (range 1 to 16 months). At the end of the study, only 4 had united, 6 had not united and one not followed up. 4 out of 7 had low Vitamin D levels, 3 out of 7 had their bisphosphonate treatment stopped and 2 had histology which showed necrotic bone with trabeculae surrounded by fibrosis. Increasing number of patients are on bisphosphonates for osteoporosis. Atypical femur fractures from bisphosphonates are often occult, often bilateral, with delayed healing. Patients on bisphosphonatetreatment should be advised to report any thigh or groin pain. Painful incomplete fractures need treatment with cephalomedullary nailing. Bone biology needs correcting by stopping bisphosphonatesand administering calcium & vitamin D supplements. Implications: We need to raise awareness amongst treating clinicians and have national guidelines

Management of the young adult hip pathologies is a special entity in orthopaedic surgical practice that needs special emphasis and consideration. A wide range of pathological and traumatic conditions occur in the young adult hip that lead to functional disability and the development of premature osteoarthritis. Proper surgical interference when the hip is still in the pre-arthritic stage restores function to the young hip and protects it from early degenerative changes, and hence the anticipated need for future joint replacement surgery is prevented. Accurate estimation of the biomechanical error combined with careful understanding of the hip joint biology is the cornerstone of success of any hip preservation surgery ever performed to save the young adult hip. Safe surgical hip dislocation approach was adopted as one of the tools in the hands of the hip preservation surgeon to treat a broad spectrum of intra-articular hip pathologies like Perthes disease and severe forms of slipped capital femoral epiphysis (SCFE). Osteo-chondroplasty at the head-neck junction with relative femoral neck lengthening for Perthes disease, and Subcapital re-orientation of severe SCFE based on its retinacular vascular pedicle are often performed via the surgical hip dislocation approach. The approach is also useful with certain types of acetabular fractures that enables fixation of dual-column fractures via single approach with intra-articular visualization for the accuracy of reduction and hardware placement. The 4 cm mini-open direct anterior approach is ideal for the surgical treatment of cases with cam and/or pincer types of femoro-acetabular impingement. Peri-articular osteotomies performed either on the acetabular or the femoral sides of the hip joint are extremely useful in the correction of the biomechanical error that led to an existing hip pathology. Periacetabular osteotomies are commonly performed to treat dysplasia of the young hip. Proximal femoral osteotomies are commonly performed to treat a wide range of hip pathologies including non-unions of femoral neck fractures in the young adult. Correction of the biomechanical error at the proper timing ensures normalization of the hip joint loading conditions and range of motion that leads to reversal of the pathologic process and prevention of osteoarthritis. A hip joint replacement would have an unknown but certainly a finite life, whereas a young hip that has healed after hip preservation surgery would definitely last for a lifetime

The inquisitive and skeptical nature of humans drives research. Questions continue to be raised from a basic, applied and clinical perspective related to our areas of interest—be it molecular biology, biomaterials, biomechanics or clinical. The future of research will only be realised by understanding the past and the planning a pathway for the future. Translating advances in the laboratory to the patient are key to improving clinical outcomes. The future holds great promise, as long as we continue to challenge ourselves and ask those fundamental questions of ‘why’ and ‘how’ things happen

Introduction. The pathophysiology of osteonecrosis of femoral head (ONFH) is uncertain for most cases with speculation of vascular impairment and changes in cell biology due to multi-factorial etiologies including corticosteroid, alcohol, smoking, trauma, radiation or caisson disease and genetic. Extracorporeal shockwave therapy (ESWT) began with an incidental observation of osteoblastic response pattern during animal studies in the mid-1980 that generated an interest in the application of ESWT to musculoskeletal disorders. The mechanism of shockwave therapy is not fully understood but several reports showed better clinical outcomes and promoted bone remodelling and regeneration effect of the femoral head after ESWT in ONFH. Therefore, we compared the clinical results of the use of extracorporeal shock wave therapy (ESWT) on the patients with ONFH in radiographic staging. Methods. We evaluated 24 patients with 32 hip joints diagnosed ONFH treated with ESWT from 1993 to 2012. Average follow-up period was 27 months, and patients were average 47.8 aged. Association Research Circulation Osseous (ARCO) staging system was used to grade radiographic stage before treatment. All the patients were divided to two groups; group 1 (ARCO stage I,II), group 2 (ARCO stage III). Comparative analysis was done between two groups with visual analogue scale (VAS) score and Harris hip score (HHS) at pre-treatment, 3, 6, 12 and 24 months after treatments. The failure was defined when radiographic stage was progressed or arthroplasty surgery was needed due to clinical exacerbation. Results. Two groups showed all clinical improvements with VAS scoring at final follow-up (group 1: mean 6.3 to 1.6, p < 0.001; group 2: mean 7.1 to 3.3, p < 0.001). With HHS, group 1 showed a significant improvement from 64.4 to 95.4 (p < 0.001), while no significance in group 2 (p = 0.280). At final-follow-up, 3 hips of group 1 and 1 hip of group 2 showed radiographic improvement, but 2 patients were performed total hip arthroplasty due to persistent pain and dysfunction. Discussion and Conclusion. ESWT could be considered as an alternative option before surgical treatment in patients not only with early stage of ONFH but also with mid stage

Osteoarthritis (OA) is the most common form of arthritis worldwide. It is a major cause of disability in the adult population with its prevalence expected to increase dramatically over the next 20 years. Although current therapies can alleviate symptoms and improve function in early course of the disease, OA inevitably progresses to end-stage disease requiring total joint arthroplasty. Mesenchymal stromal cells (MSCs) have emerged as a candidate cell type with great potential for intra-articular (IA) repair therapy. However, there is still a considerable lack of knowledge concerning their behaviour, biology and therapeutic effects. To start addressing this, we explored the secretory profile of bone marrow derived MSCs in early and end-stage knee OA synovial fluid (SF). Subjects were recruited and categorised into early [Kellgren-Lawrence (KL) grade I and II, n=12] and end-stage (KL grade III and IV, n=11) knee OA groups. The SF proteome of early and end-stage OA was tested before and three days after the addition of bone marrow MSCs (16.5×10^3, single donor) using multiplex ELISA (64 cytokines) and mass spectrometry (302 proteins detected). Non parametric Wilcoxon-signed rank test for paired samples was used to compare the levels of proteins before and after addition of MSCs in early and end-stage knee OA SF. Significant differences were determined after multiple comparisons correction (FDR) with a p<0.05. Gender distribution and BMI were not statistically different between the two cohorts (p>0.05). However, patients in early knee OA cohort were significantly younger (44.7 years, SD=7.1) than patients in the end-stage cohort (58.6 years, SD=4.4; p<0.05). In both early and end-stage knee OA, MSCs increased the levels of VEGF-A (by 320.24 pg/mL), IL-6 (by 826.78 pg/mL) and IL-8 (by 128.85 pg/mL), factors involved in angiogenesis; CXCL1/2/3 (by 103.35 pg/mL), CCL2 (by 1187.27 pg/mL), CCL3 (by 15.82 pg/mL) and CCL7 (by 10.43 pg/mL), growth factors and chemokines. However, CXCL5 (by 48.61 pg/mL) levels increased only in early knee OA, whereas PDGF-AA (by 15.36 pg/mL) and CXCL12 (by 497.19 pg/mL) levels increased only in end-stage knee OA. This study demonstrates that bone marrow derived MSCs secrete angiogenic and chemotactic factors both in early and end-stage knee OA. More importantly, MSCs show a differential reaction between early and end-stage OA. Functional assays are required to further understand on how the therapeutic effect of MSCs is modulated when exposed to OA SF

Introduction. The reconstructive hip surgeon is commonly faced with complex cases where severe bone loss makes conventional revision techniques difficult or impossible. This problem is likely to increase in future, as there is a good correlation between the degree of bone loss seen and number of previous total hip operations. In such situations, one alternative is the use impaction allografting with cement. This has captured the attention of the orthopaedic community because of its potential for reconstituting femoral bone stock. History. The first clinical reports of impaction allografting on the femoral side were in relation to revision with cementless stems. The use of morselised bone with cement on the femoral side was first reported by the Exeter group. Biology. The great enthusiasm with which this technique has been received is related to its biological potential to increase bone stock. The rapid revascularization, incorporation and remodelling of morselised compacted cancellous allograft differs dramatically from structural allografting where bone ingrowth usually is limited to 2–3 mm. Histological evidence for bony reconstitution has been presented from postmortem retrievals, and from biopsies at the time of trochanteric wire removal. Impaction allografting, performed with great attention to detail using appropriate equipment, represents an exciting reconstructive solution for contained femoral defects. Its role in larger and combined defects remains open to scrutiny. A number of technical issues with regards to allograft preparation and prosthetic design have been resolved over the past decade. The necessary intra-operative precautions are now appreciated, and the high complication rates seen in some centers have been explained in simple terms. Careful observation and cautious optimism are necessary as further refinements may well improve the predictability of the clinical results and expand the indications for this important addition to the armamentarium of the revision surgeon. The technique of impaction allografting of the femur has great potential, and is here to stay as a reconstructive solution to the deficient proximal femur in revision hip arthroplasty. Although many questions remain unanswered, the capacity for impaction allografting to act as a truly biologic augmentation of the proximal femur makes this technique the modern bridge from revision arthroplasty to reconstructive hip surgery

A randomised controlled trial was conducted using a rabbit model of a complex contaminated extremity war wound. Compared to saline soaked gauze dressings Inadine (iodine) and Acticoat (nanocrystalline silver) had significantly lower levels of Staphylococcus aureus after 7 days while Activon Tulle (Manuka honey) had significantly higher levels. Molecular level analysis of the wound was conducted. Plasma cytokines of interest were assayed using ELISA and levels of expression of relevant tissue genes measured using PCR following RNA extraction. Appreciable levels of Interleukins 4 and 6 and Tumour Necrosis Factor-α were identified in plasma with significantly higher levels of IL-4 and TNFα detected in the Activon Tulle group. In tissue TNFα, Matrix metalloproteinase-3 and the ratio of Matrix metalloproteinase-9 to Tissue Inhibitor of Matrix metalloproteinase-1 were significantly higher in tissue injured limbs than the uninjured limbs with no significant differences between groups. Interpretation of these results is challenging. IL-4 has been associated with transition from pathological inflammation to repair and TNFα with impaired healing. However, Activon Tulle had significantly higher levels of S. aureus and we found no differences in observational, histology, haematology or tissue gene expression outcomes over 7 days which would correlate with these molecular biology results

Introduction. Minimally invasive plate osteosynthesis (MIPO) is a relatively new surgical technique for the management of distal tibial fractures. Conventional open technique is unfavourable to the fracture biology because of excessive soft tissue stripping and can be associated with significant devastating complications. Objective. The aim of this study was to determine the effectiveness of the MIPO technique for distal tibial fractures. Methods. Between 2004 and 2010 twenty-nine consecutive patients had distal tibial fractures treated with MIPO by the senior author. An anteromedial plate (Synthes®) was used for all patients. Case notes and radiographs of all patients were reviewed and data, including demographics, fracture classification, complications and fracture healing were recorded on a database. Results. 29 Patients with a median age of 46 (range 25–82) were reviewed. 12 were female and 17 were male. Mean follow-up was 6.24 months. Using the AO classification there were 16 type A, 1 type B and 12 were type C fractures. Ruedi-Allgower classification showed 6 Group I fractures, 5 Group II fractures and 2 Group III fractures. There were no open fractures. 5 patients had temporary external fixation prior to MIPO. 28 patients had associated fibular fractures of which 6 required open reduction and internal fixation (through a separate surgical incision). There were no postoperative wound complications. No malunion or intraarticular displacement was noted radiographically. Two patients had delayed union but went on to heal without secondary procedures. There was 1 case of non-union. Two patients subsequently had their plates removed due to prominence of the metal work. Conclusion. We conclude that the MIPO technique is safe and effective treatment for the management of distal tibial fractures. Complications associated with MIPO are infrequent and manageable