Summary Statement

RANK is expressed in 18% of human osteosarcomas and is likely to provide additional prognostic information for clinical purposes in osteosarcoma patients at the time of diagnosis.

Primary bone tumors are rare, complex and highly heterogeneous. Its diagnostic and treatment are a challenge for the multidisciplinary team. Developments on tumor biomarkers, immunohistochemistry, histology, molecular, bioinformatics, and genetics are fundamental for an early diagnosis and identification of prognostic factors. The personalized medicine allows an effective patient tailored treatment. The bone biopsy is essential for diagnosis. Treatment may include systemic therapy and local therapy. Frequently, a limb salvage surgery includes wide resection and reconstruction with endoprosthesis, biological or composites. The risk for local recurrence and distant metastases depends on the primary tumor and treatment response. Cancer patients are living longer and bone metastases are increasing. Bone is the third most frequently location for distant lesions. Bone metastases are associated to pain, pathological fractures, functional impairment, and neurological deficits. It impacts survival and patient quality of life. The treatment of metastatic disease is a challenge due to its complexity and heterogeneity, vascularization, reduced size and limited access. It requires a multidisciplinary treatment and depending on different factors it is palliative or curative-like treatment. For multiple bone metastases it is important to relief pain and increases function in order to provide the best quality of life and expect to prolong survival. Advances in nanotechnology, bioinformatics, and genomics, will increase biomarkers for early detection, prognosis, and targeted treatment effectiveness. We are taking the leap forward in precision medicine and personalized care

The Spine Surgery Unit of IRCCS Istituto Ortopedico Rizzoli is dedicated to the diagnosis and the treatment of vertebral pathologies of oncologic, degenerative, and post-traumatic origin. To achieve increasingly challenging goals, research has represented a further strength for Spinal Surgery Unit for several years. Thanks to the close synergy with the Complex Structure Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, extensive research was carried out. The addition of the research activities intensifies a complementary focus and provides a unique opportunity of innovation. The overall goal of spine research for the Spine Surgery Unit and for the Complex Structure Surgical Sciences and Technologies is and has been to:. - investigate the factors that influence normal spine function;. - engineer and validate new and advanced strategies for improving segmental spinal instrumentation, fusion augmentation and grafting;. - develop and characterize advanced and alternative preclinical models of vertebral bone metastasis to test drugs and innovative strategies, taking into account patient individual characteristics and specific tumour subtypes so predicting patient specific responses;. - evaluate the clinical characteristics, treatment modalities, and potential contributing and prognostic factors in patients with vertebral bone metastases;. - realize customized prosthesis to replace vertebral bodies affected by tumours or major traumatic events, specifically engineered to reduce infections, and increase patients’ surgical options. These efforts have made possible to obtain important results that favour the translation of basic research to application at the patient's bedside, and from here to routine clinical practice (without excluding the opposite pathway, in which the evidence generated by clinical practice helps to guide research). Although translational research can provide patients with valuable therapeutic resources, it is not risk-free. Thus, it is therefore necessary an always close collaboration between researchers and clinicians in order to guarantee the ethicality of translational research, by promoting the good of individuals and minimising the risks

Abstract. Objectives. Ankle fractures have an incidence of around 90,000 per year in the United Kingdom. They affect younger patients following high energy trauma and, in the elderly, following low energy falls. Younger patients with pre-existing comorbidities including raised BMI or poor bone quality are also at risk of these injuries which impact the bony architecture of the joint and the soft tissues leading to a highly unstable fracture pattern, resulting in dislocation. At present, there is no literature exploring what effect ankle fracture-dislocations have on patients’ quality of life and activities of daily living, with only ankle fractures being explored. Methods. Relevant question formatting was utilised to generate a focused search. This was limited to studies specifically mentioning ankle injuries with a focus on ankle fracture-dislocations. The number of patients, fracture-dislocation type, length of follow up, prognostic factors, complications and outcome measures were recorded. Results. 939 fractures were included within the studies. Eight studies looked at previously validated foot and ankle scores, two primarily focused on the American Orthopaedic Foot and Ankle Society score (AOFAS), three on the Foot and Ankle Outcome Score (FAOS), and one study on the Olerud–Molander Score (OMAS). Patient, injury, and management factors were identified as being associated with poorer clinical outcomes. Conclusions. Not only are age and BMI a risk factor for posttraumatic osteoarthritis but they were also identified as prognostic indicators for functional outcome in this review. Patients sustaining a concurrent fracture-dislocation were found to have poorer clinical outcomes, and the timing and success of reduction further influenced outcomes. This review found that the quality of reduction was directly related to the patients’ functional outcomes post-follow up, and the risk of developing posttraumatic osteoarthritis, which was more frequent in patients sustaining Bosworth fractures, posterior malleolar fractures, and in patients over 35 years old

Purpose. Extraskeletal chondrosarcoma is a rare tumor with an indolent course and high propensity for local recurrence and metastasis. This tumor most commonly presents in the proximal extremities of middle-aged males, and is commonly asymptomatic. Although slow growing, these tumors have a significant risk of eventual relapse and metastases, especially to the lung. There are no clinical trials that investigated the best treatment options for this tumor given its very low incidence. The aim of this study is to present the surgical and clinical results of extraskeletal chondrosarcoma, which is a rare tumor. Methods. In our clinic, the information of 13 patients who were diagnosed with extra-skeletal chondrosarcoma between 2006 and 2018 were retrospectively reviewed. Demographic information, tumor size, surgical treatments, chemotherapy and radiotherapy status, follow-up times, recurrence and metastases of the patients were recorded. Results. This study included 13 patients with an average age of 53.6 ± 15 (range, 28 to 73) years diagnosed with extraskelatal chondrosarcoma. In 8 of the patients, the tumor was located in the lower limbs and it was observed that the thigh was located mostly (46.2%). The mean follow-up period of the patients was 52.8 ± 19.9 (range, 24 to 96) months. All patients underwent extensive resection and only one patient had a positive surgical margin. In the follow-up, 5 (38.5%) of the patients developed recurrence, while 6 patients had lung metastasis (46.2%) and 53.8% (7 patients) of the patients exitus. The mean tumor size was 10.4 ± 3.2 (range, 5 to 17) cm. The median survival time of the patients in the study was 61 (50.5–71.4) months. The 5-year survival rate is 51.8%. There was no significant difference between survival times according to age, gender, side, limb location, postoperative RT, recurrence and presence of lung metastasis (log rank tests p > 0.05). The cut off value for exitus obtained by ROC analysis of tumor size was determined as 11 cm (fig 1). Accordingly, the survival time of patients with 11 cm and above tumor size was observed to be statistically significantly shorter. Conclusion. Consequently, ECM is a rare soft tissue sarcoma with high local recurrence and metastasis capacity. Therefore, close follow-up is recommended. The first option should be extensive resection. Studies with large patient series on the prognostic factors of the future ECM are needed. For any figures or tables, please contact the authors directly

Spinal cord injury (SCI) is a devastating disorder for which the identification of exacerbating factors is urgently needed. Although age, blood pressure and infection are each considered to be prognostic factors in patients with SCI, exacerbating factors that are amenable to treatment remain to be elucidated. Microglial cells, the resident immune cell in the CNS, form the first line of defense after being stimulated by exposure to invading pathogens or tissue injury. Immediately after SCI, activated microglia enhance and propagate the subsequent inflammatory response by expressing cytokines, such as TNF-α, IL-6 and IL-1β. Recently, we demonstrated that the activation of microglia is associated with the neuropathological outcomes of SCI. Although the precise mechanisms of microglial activation remain elusive, several basic research studies have reported that hyperglycemia is involved in the activation of resident monocytic cells, including microglia. Because microglial activation is associated with secondary injury after SCI, we hypothesized that hyperglycemia may also influence the pathophysiology of SCI by altering microglial responses. The mice were anesthetized with pentobarbital (75 mg/kg i.p.) and were subjected to a contusion injury (70 kdyn) at the 10th thoracic level using an Infinite Horizons Impactor (Precision Systems Instrumentation). For flow cytometry, the samples were stained with the antibodiesand analyzed using a FACS Aria II flow cytometer and the FACSDiva software program (BD Biosciences). We retrospectively identified 528 SCI patients admitted to the Department of Orthopaedic Surgery at the Spinal Injuries Center (Fukuoka, Japan) between June 2005 and May 2011. The patients' data were obtained from their charts. We demonstrate that transient hyperglycemia during acute SCI is a detrimental factor that impairs functional improvement in mice and human patients after acute SCI. Under hyperglycemic conditions, both in vivo and in vitro, inflammation was enhanced through promotion of the nuclear translocation of the nuclear factor kB (NF-kB) transcription factor in microglial cells. During acute SCI, hyperglycemic mice exhibited progressive neural damage, with more severe motor deficits than those observed in normoglycemic mice. Consistent with the animal study findings, a Pearson χ2 analysis of data for 528 patients with SCI indicated that hyperglycemia on admission (glucose concentration ≥126 mg/dl) was a significant risk predictor of poor functional outcome. Moreover, a multiple linear regression analysis showed hyperglycemia at admission to be a powerful independent risk factor for a poor motor outcome, even after excluding patients with diabetes mellitus with chronic hyperglycemia (regression coefficient, −1.37; 95% confidence interval, −2.65 to −0.10; P < 0.05). Manipulating blood glucose during acute SCI in hyperglycemic mice rescued the exacerbation of pathophysiology and improved motor functional outcomes. Our findings suggest that hyperglycemia during acute SCI may be a useful prognostic factor with a negative impact on motor function, highlighting the importance of achieving tight glycemic control after central nervous system injury

Background. People with back pain often experience long-term pain with recurrences and fluctuations. However, few studies have considered which factors predict long-term outcomes. Purpose. To determine the prognostic factors, measured around the time of a primary care back pain consultation, that predict clinically significant pain in both the short (6 months) and long-term (5 years). Methods. Back pain consulters at 8 GP practices received a questionnaire shortly after consultation. Information was collected on potential prognostic factors: demographics (age, gender, educational, social class), physical (pain, disability, pain duration, distal leg pain), psychological (illness perceptions, coping, fear avoidance, pain self-efficacy, depression, anxiety) and occupational (work status). Patients were followed-up by postal questionnaire 6 months and 5 years later. The Chronic Pain Grade was used to define clinically significant pain at outcome. Results. Baseline pain intensity (Relative Risk (RR) 1.12, 95% CI 1.03, 1.20) and a strong patient belief that their LBP would last a long time (RR 1.04, 95% CI 1.01, 1.07) predicted outcome at 6 months. Outcome at 5 years was best predicted by a similar model: pain intensity (RR 1.09, 95% CI 0.997, 1.20) and a strong belief that their back pain would persist (RR 1.06, 95% CI 1.03, 1.09). Conclusion. Pain intensity and a belief by the patient that their back pain will last a long time predicted clinically significant pain in both the short and long-term. Both predictors have the potential for clinical intervention at the consultation stage. No conflicts of interest. Source of funding: The baseline and 6-month follow-up phases of this study was supported financially by a Programme Grant awarded by the Arthritis Research UK [13413] and the 5-year follow-up phase was completed as part of Dr KM Dunn's Wellcome Trust Grant [083572]. This abstract has not been previously published in whole or substantial part nor has it been presented previously at a national meeting

Introduction. Osteonecrosis of the femoral head usually progresses to collapse in up to 70% to 80% of all cases. Previous studies have shown high failure rates with non-operative treatment, whereas, some surgical options including bone grafting, core decompression, osteotomy and arthroplasty have been recommended. Total hip arthroplasty and hemiarthroplasty, either cemented or cementless, are the last resort for improving the functional outcomes for the elderly. However, salvage of the femoral head in relatively young patients is widely advocated. Thus vascularized bone grafting has been recommended to salvage the collapsing femoral head. The purpose of this study was to evaluate the prognostic factors related to the outcome of the vascularized iliac bone grafting in the treatment of osteonecrosis of the femoral head. Methods. A retrospective case series review study is presented. Between April 1987 and April 2003, 47 patients (51 hips) in the authors' hospital underwent vascularized iliac bone grafting for the treatment of osteonecrosis of the femoral head. Three patients were lost to follow-up, thus, 44 patients (48 hips), 38 men and 4 women, were included in the study. All patients underwent operation by one experienced senior surgeon. Patients were grouped according to related risk factors, i.e., trauma, corticosteroid, alcohol, and an idiopathic group. A radiographic scale, the Ficat and Arlet classification system, was used for grading the osteonecrosis. We set the conversion to total hip arthroplasty as the end point for survival of vascularized iliac bone grafting in this study. Kaplan-Meier survivorship analysis was used to determine the significance with regard to the risk factors, age, Ficat and Arlet staging, gender, and side. Results. The Kaplan-Meier survivorship analysis showed that the 5-year overall rate of graft survival was 68.5% (95% confidence interval: 52.7% to 80.0%), 10-year overall rate of graft survival was 61.5% (95% confidence interval: 44.4% to 74.8%), and 61.5% (95% confidence interval: 44.4% to 74.8%) at 15 years. There was no significant difference between the groups regarding the prognostic factors of etiology, gender, side, and stage. The only significant parameter was the age that the patients older than 50 years had the worst 5-year survival rate of the femoral head (p<0.05). Conclusion. Vascularized bone grafting is a technically demanding procedure when compared to conventional core decompression or arthroplasty. However, this technique can preserve the femoral head from collapse and preclude the need for arthroplasty in young patients

Osteochondral (OC) grafting is one available method currently used to repair full thickness cartilage lesions with good results clinically when grafting occurs in patients with specific positive prognostic factors. However, there is poor understanding of the effect of individual patient and surgical factors. With limited tissue availability, development of Finite Element (FE) models taking into account these variations is essential. The aim of this study was to evaluate the effect of altering the material properties of OC grafts and their host environment through computer simulation. A generic FE model (ABAQUS CAE 2017) of a push-out test was developed as a press-fit bone cylinder (graft) sliding inside a bone ring (host tissue). Press-fit fixation was simulated using an interference fit. Overlap between host and graft (0.01mm–0.05mm) and coefficient of friction (0.3–0.7) were varied sequentially. Bone Young's moduli (YM) were varied individually between graft and host within the range of otherwise derived tissue moduli (46MPa, 82MPa, 123MPa). Increasing both overlap and frictional coefficient increased peak dislodging force independently (overlap: 490% & frictional coefficient: 176% across range tested). Increasing bone modulus also increased dislodging force, with host bone modulus (107%, 128%, and 140% increase across range, when Graft YM = 123MPa, 82 MPa, and 46MPa, respectively) having a greater influence than graft modulus (28%, 19% and 10% increase across range, when Host YM = 123 MPa, 82MPa and 46MPa, respectively). As anticipated increasing overlap and friction caused an increase in force necessary to dislodge the graft. Importantly, differentially changing the graft and host material properties changed the dislodging force indicating that difference between graft and host may be an important factor in the success or failure clinically of osteochondral grafting

Purpose. Addressing posterior tibial plateau fractures is increasingly recognized as an important prognostic factor for functional outcome. The treatment of posterior tibial plateau fractures is rather demanding and the implants are still standard, off-the-shelf implants. This emphasizes the need for a more thorough morphological study of the posterior tibial plateau, in order to treat these posterior fractures more adequately. We aimed to demonstrate anatomical variations of the tibia in order to develop better implants. Method. After approval of the ethical committee 22 historically available CT scans of intact left tibia”s were segmented using Mimics (Materialise, Belgium). In order to perform principal component analysis, corresponding meshes are necessary. Mesh correspondence was achieved by deforming one selected source tibia to every other target tibia, through non rigid registration. The non-rigid registration algorithm was based on the algorithm described by Amberg et al (ref). After performing the non-rigid registration, principal component analysis was performed in Matlab (Mathworks, USA). Results. The first 3 components account for 98,1% of the anatomical shape variation of the tibia. The first principal component accounts for 95,4, the second accounts for 1,6% and the third component accounts for the remaining 1,1% of variation. In the first principal component the most marked variation was the length and the shaft width. Shorter tibia”s have a steeper and more angled posterior medial and lateral plateau as where longer tibia”s have a more rounded posterior tibia plateau. On the distal end, the tip of the medial malleolus is more prominent in shorter tibia”s than in longer tibia”s. The orientation of the tibiofibular joint is directed more posteriorly in larger tibias where it is orientated more laterally in smaller tibia”s. The slope of the medial and lateral tibia plateau is not related to the length or width of the plateau. The second principal component shows a relationship between a valgus shaped tibia shaft and its relation to a relatively smaller medial plateau”s compared with straight tibia”s of the same length. Valgus shaped, small tibia shafts have more posteriorly tilted lateral plateau”s compared with straight, broad shafted tibias. The third principal component shows that an angular shaped posterior tibia plateau is related to a more increased anterior bowing. The increase in the posterior tilt is mostly marked in the medial tibia plateau. Conclusion. The majority of tibia shape variations is directly related to the length of the shaft. The clinically known varus and valgus deformations represent only a small percentage of the total variation. Nevertheless, their variation within the second component is large and has a direct relation to the morphology of the tibia plateau. This data coud furthermore be used to improve implant design

Metastatic osteosarcoma is seen in 10-20% of patients at initial presentation with the lung the most common site of metastasis. Historically, prognosis has been poor. We studied trends in survival in our small developed nation and aimed to identify correlations between the survival rate and three factors: newer chemotherapy, advances in radiological imaging and a more aggressive approach adopted by cardiothoracic surgeons for lung metastases. Our national bone tumour registry was used to identify patients at the age of 18 or under, who presented with metastatic disease at initial diagnosis between 1933 and 2006. There were 30 patients identified. Kaplan-Meier analysis was used to determine survival rates and univariate analysis was performed using the Cox regression proportional hazards model. Median survival has improved over the last 50 years; highlighted by the ‘Kotz’ eras demonstrating incremental improvement with more effective chemotherapy agents (p=0.004), and a current 5-year survival of 16%. Aggressive primary and metastatic surgery also show improving trends in survival. Three patients have survived beyond 5 years. The introduction of computerised tomography scanning has led to an increase in the prevalence of metastases at initial diagnosis. Metastatic osteosarcoma remains with a very poor prognostic factor, however, aggressive management has been shown to prolong survival

Objectives

Given the function of adiponectin (ADIPOQ) on the inflammatory condition of obesity and osteoarthritis (OA), we hypothesized that the ADIPOQ gene might be a candidate gene for a marker of susceptibility to OA.

Objectives

The clinical utility of routine cross sectional imaging of the abdomen and pelvis in the screening and surveillance of patients with primary soft-tissue sarcoma of the extremities for metastatic disease is controversial, based on its questionable yield paired with concerns regarding the risks of radiation exposure, cost, and morbidity resulting from false positive findings.