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Background: It remains unknown whether there is a causal relationship between intraoperative hypotension and postoperative neurocognitive disorders. We tested the hypothesis that personalised—compared to routine—intraoperative blood pressure management reduces the incidence of postoperative neurocognitive disorders in patients having major noncardiac surgery. Methods: In this single-centre trial, 328 elective major noncardiac surgery patients were randomly allocated to receive personalised blood pressure management (i.e. maintaining intraoperative mean arterial pressure [MAP] above preoperative baseline MAP from automated 24-h blood pressure monitoring) or routine blood pressure management (i.e. maintaining MAP above 65 mm Hg). The primary outcome was the incidence of neurocognitive disorders (composite of delayed neurocognitive recovery and delirium) between postoperative days 3 and 7. Results: The primary outcome, neurocognitive disorders, occurred in 18 of 147 patients (12%) assigned to personalised and 21 of 148 patients (14%) assigned to routine blood pressure management (odds ratio [OR]=0.84, 95% confidence interval [CI]: 0.40–1.75, P=0.622). Delayed neurocognitive recovery occurred in 17 of 146 patients (12%) assigned to personalised and 17 of 145 patients (12%) assigned to routine blood pressure management (OR=0.99, 95% CI: 0.45–2.17, P=0.983). Delirium occurred in 2 of 157 patients (1%) assigned to personalised and 4 of 158 patients (3%) assigned to routine blood pressure management (OR=0.50, 95% CI: 0.04–3.53, P=0.684). Conclusions: Personalised intraoperative blood pressure management maintaining preoperative baseline MAP neither reduced the incidence of the composite primary outcome neurocognitive disorders between postoperative days 3 and 7 nor the incidences of the components of the composite primary outcome—delayed neurocognitive recovery and delirium—compared to routine blood pressure management in patients having major noncardiac surgery. Clinical trial registration: ClinicalTrials.gov (NCT03442907).

Abstract Osteoarthritis represents a chronic degenerative joint disease with exceptional clinical relevance. Polymorphisms of the CALCA gene, giving rise to either a procalcitonin/calcitonin (PCT/CT) or a calcitonin gene-related peptide alpha (αCGRP) transcript by alternative splicing, were reported to be associated with the development of osteoarthritis. The objective of this study was to investigate the role of both PCT/CT and αCGRP transcripts in a mouse model of post-traumatic osteoarthritis (ptOA). WT, αCGRP −/− and CALCA −/− mice were subjected to anterior cruciate ligament transection (ACLT) to induce ptOA of the knee. Mice were sacrificed 4 and 8 weeks post-surgery, followed by micro-CT and histological evaluation. Here we show that the expression of both PCT/CT and αCGRP transcripts is induced in ptOA knees. CALCA −/− mice show increased cartilage degeneration and subchondral bone loss with elevated osteoclast numbers compared to αCGRP −/− and WT mice. Osteophyte formation is reduced to the same extent in CALCA −/− and αCGRP −/− mice compared to WT controls, while a reduced synovitis score is noticed exclusively in mice lacking CALCA. Our data show that expression of the PCT/CT transcript protects from the progression of ptOA, while αCGRP promotes osteophyte formation, suggesting that CALCA-encoded peptides may represent novel targets for the treatment of ptOA.

Abstract Purpose There is a high risk of increasing the posterior tibial slope (PTS) during medially opening‐wedge high tibial osteotomy (mowHTO). Most recently, the idea of intentional simultaneous coronal and sagittal correction, using uniplanar cutting techniques has emerged. This study aims to examine the influences of variable hinge positioning and osteotomy gap height on the sagittal and coronal plane. Methods Twenty uniplanar mowHTOs were performed in standardised (left) solid‐foam proximal tibia models. In the different models, hinge position was rotated stepwise by 10°, between 90° (cutting straight medial to lateral) and 0° (cutting straight anterior to posterior) (n = 10). Additionally, gap heights of 5 and 10 mm were produced and analysed. Logistic regression analysis was performed to calculate a predictive regression formula for the relation between gap height, hinge rotation and the changes of medial proximal tibia angle (MPTA), medial and lateral PTS. Results Between cutting angles of 90 and 20°, the MPTA was mainly influenced by the gap height (0.95° MPTA per 1 mm gap height), but not by the cutting angle. Between 20 and 0°, the MPTA was decreased by 3.6° per 10° of rotation, but not by the gap height. Between cutting angles of 90 and 10°, the PTS was increased linearly by 0.97° per 10° of rotation and by 0.61° per 1 mm gap height. Conclusion In mowHTO with lateral hinge positions, the MPTA is mainly influenced by gap height. Changes of PTS can be avoided by a straight lateral hinge position. In posterior hinge locations (0‐20°), changes of MPTA are mainly caused by hinge rotation, but not by gap height. Level of Evidence Level III, Case–control study.

Abstract Proximal femur fractures (PFF) are a common injury in elderly patients that significantly impact mobility and daily living activities. Mortality rates in this population are also high, making effective treatment essential. Recent advances in intensive and geriatric care have enabled complex surgical interventions that were previously not feasible. However, there is a lack of studies focusing on outcome parameters in very elderly patients (≥ 90 years) who receive intensive care treatment following PFFs. In this retrospective study, we analyzed multi-layered data of 148 patients who were 90 years or older and received intensive care after trauma and orthopedic surgical treatment for PFFs or periprosthetic fractures between 2009 and 2019. All patients received a 365-day follow-up. To identify potential predictors of mortality, all deceased and surviving patients were subjected to multiple logistic regression analyses. We found that 22% of patients deceased during in-hospital care, and one-year survival was 44%. Independent predictors of one-year all-cause mortality included higher CCI and SOFA scores at ICU admission. Overall, 53% of patients who resided in private dwellings prior to admission were able to return home. Our study highlights the utility of using CCI and SOFA scores at ICU admission as prognostic indicators in critically ill very elderly patients who undergo surgical treatment for PFFs. These scores can provide valuable insight into the severity of illness and potential outcomes, which can inform resource allocation, prioritize endangered patients, and aid in end-of-life discussions and planning with patients and their families. Our findings can help improve the management of PFFs in very elderly patients and contribute to optimized patient care.

Abstract Background Minimally invasive approaches to the hip joint for total hip arthroplasty such as the DAA (“Direct Anterior Approach with bikini incision”) are increasingly utilized. According to the literature, this approach is more muscle-sparing, results in less postoperative pain, and achieves higher patient satisfaction. The existence of postoperative lymphedema after hip arthroplasty is hardly considered. The aim of this paper is to contribute to the evaluation of the different access methods related to postoperative lymphedema and their functional outcomes. Methods This is a prospective non-randomized study at an orthopedic specialist clinic in Northern Europe. The surgeons that performed the arthroplasties are high-volume surgeons in private practice affiliated to the clinic. The study included 188 patients with primary hip arthroplasty in a 1:1 ratio (DAA: standard accesses (posterior, transgluteal, and anterolateral access)). Epidemiologic data, Harris Hip Score, Oxford Hip Score, European Quality of Life 5, and Visual Analog Scale were collected preoperatively on admission day, 3rd and 5th postoperative day, and follow-up after 1 year. Furthermore, the range of motion, gait, and ability to climb stairs, as well as the presence of hypesthesia were assessed. To evaluate the edema situation, both legs were measured on the 3rd and 5th postoperative day. The prescription of manual lymphatic drainage and remaining swelling conditions 1 year postoperatively were recorded. Results For each group, 94 patients with a mean age of 61.7 years (DAA 60.7 and standard access 62.6) were included. All but one patient in the DAA group showed postoperative lymphedema (n: 93/94; 98.9%). In the standard surgery group, only n: 37/94 (39.4%) showed swelling symptoms requiring treatment. After 1 year, lymphedema persisted in 20 patients in the DAA group and 0 patients in the standard-OR group. Hypesthesia at the ventral thigh persisted in 16/94 (= 17%) patients of the DAA group versus 0/94 patients of the standard group after 12 months. Of these 16 cases, 10 had concomitant edema (62.5%). The DAA showed better results than the standard accesses in terms of Oxford Hip Score (p 0.05). Conclusion The present study demonstrated the increased incidence of postoperative lymphedema in patients operated on via DAA access using a Bikini-type skin incision. In the follow-up, significantly more hypesthesia of the ventral thigh occurred in the DAA group. Otherwise, the DAA proved to be superior to the standard approaches from a functional point of view at short-term follow-up. Future research is needed to compare the horizontally oblique to the longitudinal oblique skin incision technique in direct anterior hip surgery regarding the above-mentioned adverse effects found in this study.

Abstract A clear recommendation regarding treatment strategy of fragility fractures of the pelvic ring is missing. The most typical fracture pattern is a lateral compression type injury with non-displaced fractures of the anterior pubic rami and a unilateral os sacrum fracture (FFP II). We hypothesized that operative treatment would be superior to conservative treatment. From October 2017 to April 2020, a randomized prospective non-blinded trial with n = 39 patients was carried out. Two arms with 17 operative versus 22 conservative cases were created. Inclusion criteria were a posterior pelvic ring fracture FFP type II, age over 60 years and acute fracture (

Abstract Background The combined injury of the medial collateral ligament complex and the anterior cruciate ligament (ACL) is the most common two ligament injury of the knee. Additional injuries to the medial capsuloligamentous structures are associated with rotational instability and a high failure rate of ACL reconstruction. The study aimed to analyze the specific pattern of medial injuries and their associated risk factors, with the goal of enabling early diagnosis and initiating appropriate therapeutic interventions, if necessary. Results Between January 2017 and December 2018, 151 patients with acute ACL ruptures with a mean age of 32 ± 12 years were included in this study. The MRIs performed during the acute phase were analyzed by four independent investigators—two radiologists and two orthopedic surgeons. The trauma impact on the posterolateral tibial plateau and associated injuries to the medial complex (POL, dMCL, and sMCL) were examined and revealed an injury to the medial collateral ligament complex in 34.4% of the patients. The dMCL was the most frequently injured structure (92.2%). A dMCL injury was significantly associated with an increase in trauma severity at the posterolateral tibial plateau (p

Abstract Notch signaling regulates cell fate in multiple tissues including the skeleton. Hajdu–Cheney-Syndrome (HCS), caused by gain-of-function mutations in the Notch2 gene, is a rare inherited disease featuring early-onset osteoporosis and increased risk for fractures and non-union. As the impact of Notch2 overactivation on fracture healing is unknown, we studied bone regeneration in mice harboring a human HCS mutation. HCS mice, displaying high turnover osteopenia in the non-fractured skeleton, exhibited only minor morphologic alterations in the progression of bone regeneration, evidenced by static radiological and histological outcome measurements. Histomorphometry showed increased osteoclast parameters in the callus of HCS mice, which was accompanied by an increased expression of osteoclast and osteoblast markers. These observations were accompanied by inferior biomechanical stability of healed femora in HCS mice. Together, our data demonstrate that structural indices of bone regeneration are normal in HCS mice, which, however, exhibit signs of increased callus turnover and display impaired biomechanical stability of healed fractures.

Summary: Impaired fracture healing is of high clinical relevance, as up to 15% of patients with long-bone fractures display non-unions. Fracture patients also include individuals treated with selective norepinephrine reuptake inhibitors (SNRI). As SNRI were previously shown to negatively affect bone homeostasis, it remained unclear whether patients with SNRI are at risk of impaired bone healing. Here, we show that daily treatment with the SNRI reboxetine reduces trabecular bone mass in the spine but increases cortical thickness and osteoblast numbers in the femoral midshaft. Most importantly, reboxetine does not impair bone regeneration in a standardized murine fracture model, and even improves callus bridging and biomechanical stability at late healing stages. In sum, reboxetine affects bone remodeling in a site-specific manner. Treatment does not interfere with the early and intermediate stages of bone regeneration and improves healing outcomes of the late-stage fracture callus in mice.

Abstract Background Patella fractures account for approximately 1% of all skeletal injuries. Treatment options are vast and no definitive conclusion on what option is the most beneficial could be made so far. Plate osteosynthesis appears to gain in importance. We aim to give insight into the more recent trends and developments as well as establish the epidemiology of patella fractures in Germany by analysing treatment and epidemiological data from a national database. Methods Anonymised data was retrieved form a national database. In the period of 2006 to 2020, all patients with patella fractures as defined in ICD-10 GM as their main diagnosis, who were treated in a German hospital were included. Patients were divided into subgroups based on gender and age. Age groups were created in 10-year intervals from 20 years old up to 80 years old with one group each encompassing all those above the age of 80 years old and below 20 years old and younger. Linear regression was performed were possible to determine statistical significance of possible trends. Results A total of 151,435 patellar fractures were reported. 95,221 surgical interventions were performed. Women were about 1.5 times more likely to suffer from patella fracture than men. The relative number of surgical interventions rose from about 50% in 2006 to 75% in 2020. Most surgical interventions are performed in those over the age of 50. The incidence of complex fractures and plate osteosynthesis has significantly increased throughout the analysed period. Conclusions We found a clear trend for surgical treatment in Germany with an increase in surgical procedures. We could also show that this ratio is age-related, making it more likely for younger patients in the age groups from 0 to 70 years old to receive surgical treatment for their patella fracture.

Abstract Since the introduction of widely available e-scooter rentals in Hamburg, Germany in June of 2019, our emergency department has seen a sharp increase in the amount of e-scooter related injuries. Despite a rising number of studies certain aspects of e-scooter mobility remain unclear. This study examines the various aspects of e-scooter associated injuries with one of the largest cohorts to date. Electronic patient records of emergency department admissions were screened for e-scooter associated injuries between June 2019 and December 2021. Patient demographic data, mechanism of injury, alcohol consumption, helmet usage, sustained injuries and utilized medical resources were recorded. Overall, 268 patients (57% male) with a median age of 30.3 years (IQR 23.3; 40.0) were included. 252 (94%) were e-scooter riders themselves, while 16 (6%) were involved in crashes associated with an e-scooter. Patients in non-rider e-scooter crashes were either cyclists who collided with e-scooter riders or older pedestrians (median age 61.2 years) who tripped over parked e-scooters. While e-scooter riders involved in a crash sustained an impact to the head or face in 58% of cases, those under the influence of alcohol fell on their head or face in 84% of cases. This resulted in a large amount of maxillofacial soft tissue lacerations and fractures. Extremity fractures and dislocations were more often recorded for the upper extremities. This study comprises one of the largest cohorts of e-scooter associated injuries to date. Older pedestrians are at risk to stumble over parked e-scooters. E-scooter crashes with riders who consumed alcohol were associated with more severe injuries, especially to the head and face. Restricted e-scooter parking, enforcement of drunk driving laws for e-scooters, and helmet usage should be recommended.

Abstract Background It is known that specimen collection followed by histopathological workup is the core of evidence-based medical therapy of musculoskeletal tumors. There exist many controversies about how a biopsy should be performed. While some centers recommend minimal invasive biopsy procedures, mostly the core needle biopsy (CNB), others prefer the incisional biopsy. Purpose of the study This study aimed to determine the accuracy of incisional biopsy for malignant tumors in the musculoskeletal system. Moreover, advantages and disadvantages to other biopsy methods are discussed. Methods This retrospective, single-center study about 844 incisional biopsies (benign and malignant) analysis the diagnostic accuracy of 332 malignant tumors, concerning the final histopathological result. In addition, surgical complications are analyzed to find the best way to plan and treat patients timely and correct. Secondary endpoints are the patients age, the pure operation time, as well as the type of tumor, and the subsequent therapy. Results In summary, incisional biopsy corresponded a sensitivity of 100% for malignancy in 844 incisional biopsies and a specificity of 97.6% in 332 malignant tumors, but it features greater operative expense (incision/suture 23.5 min) and the risk of general anesthesia. Conclusion The method of biopsy should be tailored to the individual patient and the experience of the center performing the procedure.

Soft tissue sarcomas are malignant diseases with a complex classification and various histological subtypes, mostly clinically inconspicuous appearance, and a rare occurrence. To ensure safe patient care, the European Society of Musculoskeletal Radiology (ESSR) issued a guideline for diagnostic imaging of soft tissue tumors in adults in 2015. In this study, we investigated whether implementation of these guidelines resulted in improved MRI protocol and report quality in patients with soft tissue sarcomas in our cancer center. All cases of histologically confirmed soft tissue sarcomas that were treated at our study center from 2006 to 2018 were evaluated retrospectively. The radiological reports were examined for their compliance with the recommendations of the ESSR. Patients were divided into two groups, before and after the introduction of the 2015 ESSR guidelines. In total, 103 cases of histologically confirmed sarcomas were studied. The distribution of, age, gender, number of subjects, performing radiology, and MRI indication on both groups did not show any significant differences. Only using the required MRI sequences showed a significant improvement after the introduction of the guidelines (p = 0.048). All other criteria, especially the requirements for the report of findings, showed no improvement. The guidelines of the European Society for Musculoskeletal Radiology are not regularly followed, and their establishment did not consistently improve MRI quality in our study group. This poses a risk for incorrect or delayed diagnosis and, ultimately, therapy of soft tissue tumors. However, this study is the first of its kind and involves a limited collective. A European-wide multicenter study would be appreciated to confirm these results.

Abstract Background According to guidelines, every soft tissue tumor (STT) larger than 3 cm should be biopsied before definitive resection. Advances in magnetic resonance imaging (MRI) improve the possibility to give a provisional diagnosis of the tumor’s entity. Can lipomas and atypical lipomatous tumors (ALTs) of the extremities therefore be primarily marginally resected based on interpretation of MR images without a previous biopsy?. Methods In this retrospective, single-center study, 240 patients with the suspicion of a lipomatous tumor in MRI and surgical treatment in our institution between 2011 and 2020 were included. MR imaging was performed before surgery. All resected specimens underwent histopathological analysis. Results The collective comprised 142 tumors that were suspected as lipoma or ALT by the radiologist and underwent primary marginal resection (PMR). One case had myxoid liposarcoma that was underestimated on MRI and needed radical follow-up resection. One-hundred forty-one patients were cured after PMR. Ninety-eight patients were biopsied initially and in 93 cases resected afterwards according to the necessary oncological margins. Conclusion In our institution, PMR is performed if a lipoma or ALT is suspected on MR imaging. Our treatment method and the diagnostic algorithm are presented. Primary resection spares patients from one surgical procedure, but a slight risk for underestimation of the tumor remains.

Abstract Background Lumps and soft tissue tumors (STT) are frequent reasons for consulting a physician. Most STT are benign, and lumps are not always associated with a tumor. MRI is the most advanced imaging modality to assist a provisional diagnosis of STT. Only a small fraction of STT is malignant, these soft tissue sarcomas are known for their aggressive growth. The study aims to analyze the influence of the MRI report on the speed of treatment of patients with suspected STT. Methods This was a retrospective, longitudinal, single-center study from 2011–2020. We included adult patients who had biopsies or resections of masses suspicious for STT in MRI exams. MRI reports were classified as benign (I), intermediate/unclear (II), or malignant (III). For these cohorts, time was statistically analyzed from MRI scan to first contact with the University cancer center (UCC) and surgery. Furthermore, distance in kilometers from the patients´ home to the UCC was examined and compared to age and suspected malignancy. Results Three hundred two patients (♀130; ♂172) were included. Histologic analyses revealed 286 tumors. The average age of the patients was 54.7(SD: 16.2) years. Malignant tumors were more often suspected in older patients (p = 0.0098). Patients with a benign diagnosed tumor in MRI contacted the UCC after an average of 31.3 (SD: 47.8) days. In contrast, patients with suspicion of a malignant tumor contacted the UCC significantly earlier, after 14.1 days (SD: 17.1); p = 0.0098. Likewise, the time between first contact and biopsy/resection was 32.8 days (SD: 35.7) for suspiciously benign tumors, and potentially malignant tumors were treated significantly faster 14.8 (SD: 16.0) days; (p = 0.028). Patients traveled on average 47.5 km (range: 0.5–483) to contact a specialized physician at the UCC. Suspected degree of malignancy or patient´s age had no statistical influence on traveled distance. Discussion The treatment speed depended to a great extent on the suspected malignancy of the STT in the MRI report. The provisional diagnoses from the radiologist highly influenced the time delay between MRI scan and first contact to the UCC and surgical treatment. No discrimination of age or distance to the UCC was observed in this study.

Abstract Intermittent injections of parathyroid hormone (iPTH) are applied clinically to stimulate bone formation by osteoblasts, although continuous elevation of parathyroid hormone (PTH) primarily results in increased bone resorption. Here, we identified Calca, encoding the sepsis biomarker procalcitonin (ProCT), as a novel target gene of PTH in murine osteoblasts that inhibits osteoclast formation. During iPTH treatment, mice lacking ProCT develop increased bone resorption with excessive osteoclast formation in both the long bones and axial skeleton. Mechanistically, ProCT inhibits the expression of key mediators involved in the recruitment of macrophages, representing osteoclast precursors. Accordingly, ProCT arrests macrophage migration and causes inhibition of early but not late osteoclastogenesis. In conclusion, our results reveal a potential role of osteoblast-derived ProCT in the bone microenvironment that is required to limit bone resorption during iPTH.

Introduction. Apps, in general, are an integral part of our daily lives. To investigate the current usage behaviour of trauma surgeons and radiologists regarding medical apps in clinical practice and to find out if and how the current range of medical apps can be improved, we surveyed trauma surgeons and radiologists in northern Germany. Material and Methods. An online questionnaire was sent to 100 trauma surgeons and 100 radiologists in northern Germany. Participants were asked about the frequency of their use of medical apps in clinical practice, which apps were used most often, how useful participants thought apps were, and in which area they would like to see improvements. The most frequently mentioned apps were finally analyzed. Results. The survey study showed that 87.4% of the trauma surgeons and 67.4% of the radiologists use medical apps on a regular basis at work. It also revealed that trauma surgeons used medical apps much more often than radiologists and that young doctors were more likely to rely on medical apps than chief physicians. 80.0% of the participants would pay at least 5 euros for a medical app. Trauma surgeons see the greatest need for support in their daily work from medical apps in the area of treatment, while radiologists seek more support in the area of classification. Conclusion. The study underscored the broad acceptance of medical apps in everyday clinical practice. As the physicians are willing to spend money and stated a general interest and need for further developments, there is high potential for the future. This trial is registered with DRKS00026766.

Traumatic or iatrogenic sciatic nerve injury, but not superior gluteal nerve injury, is a well described complication after acetabular fractures. Most often, sciatic nerve injuries occur in fractures involving the posterior column/wall with a hip dislocation and posterior fracture displacement resulting in narrowing of the greater sciatic foramen and injuring the sciatic nerve passing through. In this case report, a case of abductor mechanism deficiency with positive Trendelenburg's sign after an acetabular fracture of the posterior column with hip dislocation is presented. Postoperative clinical and MRI examination revealed a neurogenic atrophy of gluteus medius and minimus muscles suggesting a superior gluteal nerve injury due to initial subtotal incarceration of the greater sciatic foramen by a displaced posterior fracture fragment. An additional mild sciatic nerve injury resolved in the early postoperative course, while intensive physiotherapy improved the patient's complaints and muscular atrophy caused by the superior gluteal nerve injury within 12 months. This case report intends to raise awareness for rare neurological complications after acetabular fractures for their early detection.

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality.Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children

Abstract Background Surgical site infection (SSI) occurs in 3–10 % of patients with surgically treated tibial plateau fractures. This study aimed to evaluate the impact of SSI on patients’ outcome after fixation of tibial plateau fractures. Methods We conducted a retrospective multicenter study in seven participating level I trauma centers between January 2005 and December 2014. All participating centers followed up with patients with SSI. In addition, three centers followed up with patients without SSI as a reference group. Descriptive data and follow-up data with patient-reported outcome scores (Knee Injury and Osteoarthritis Outcome Score [KOOS] and Lysholm knee scoring scale score) were evaluated. Results In summary, 287 patients (41 with SSI and 246 without SSI; average 50.7 years) with an average follow-up of 75.9 ± 35.9 months were included in this study. Patients with SSI had a significantly poorer overall KOOS (KOOS5) (48.7 ± 23.2 versus [vs.] 71.5 ± 23.5; p

Background: Surgical therapy of bone metastases is becoming increasingly important due to prolonged life expectancy and improved oncological treatment options. In a mostly palliative approach, it is necessary to identify those patients who might benefit from surgery. The shorter the remaining lifetime, the more restricted the indication and the less radical the intervention should be. The aim of this study was to evaluate the postoperative outcomes and prognostic factors for survival of patients with surgically treated bone metastases. Methods: We retrospectively included 140 patients who underwent surgery for 151 bone metastases in the extremities and pelvis at our hospital between 2010 and 2020. We examined patient demographics, surgical procedures, 30-day complications, local tumour progression, and reoperations. Survival was calculated using Kaplan-Meier analysis. Prognostic factors were investigated by univariate analysis using the log-rank test and multivariate analysis using the Cox regression hazard model. Results: In 138 patients, the median survival time was 12.3 months. The overall survival rates at one, two, three and five years were 52.3%, 37.6%, 28.0%, and 18.0%, respectively. In univariate analysis, lung cancer, renal cell carcinoma, pathological fracture, visceral metastasis and multiple bone metastases were significantly associated with prognosis. No significant influence was determined for gender, age, location of bone metastasis, type of surgical procedure and time between diagnosis of primary tumour and surgery for bone metastasis. Multivariate analysis confirmed that pathological fracture, visceral metastasis and lung cancer were negative prognostic variables in terms of survival. Within 30 days, the incidence of complications was 25.0% and mortality was 9.3%. The most common complications were urinary tract infections (5.0%), pneumonia (4.3%), and delirium (2.9%). Local tumour progression occurred in 12 patients (8.7%) and five reoperations (3.6%) were performed. There were no significant differences between patients treated with endoprosthetic replacement (n = 47) and those treated with internal fixation (n = 91) in terms of 30-day complications and mortality as well as local tumour progression. Conclusions: Survival of patients after surgery for bone metastases in the extremities or pelvis is very limited. The presence of a pathological fracture, visceral metastasis and lung cancer were independent prognostic factors for poor survival. Both internal fixation and endoprosthetic replacement achieved similar outcomes.

Osteoid osteoma (OO) is a benign bone tumor that rarely occurs in the bones of the hand. Due to the comparatively non-specific symptoms when occurring in the hand, OO is often misdiagnosed at first presentation, posing a diagnostic challenge. In the present case study, six cases of phalangeal and carpal OO, treated surgically at our department between 2006 and 2020, were retrospectively reviewed. We compared all cases regarding demographic data, clinical presentation, imaging findings, time to diagnosis, surgical treatment, and clinical outcome in follow-up examinations. When OO occurs in the bones of the hand, it can lead to swelling and deformities, such as enlargement of the affected bone and nail hypertrophy. Initial misdiagnoses such as primary bone tumors other than OO, tendinitis, osteomyelitis, or arthritis are common. Most of the presented cases showed a prolonged time until diagnosis, whereby the primarily performed imaging modality was often not sensitive. CT proved to be the most sensitive sectional imaging modality for diagnosing OO. With adequate surgical treatment, complications and recurrence are rare.

Objectives Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs.Design A multicentre, international, collaborative cohort study.Setting 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020.Participants Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, Hodgkin lymphoma, Wilms’ tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer.Main outcome measure All-cause mortality at 30 days and 90 days.Results 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p

Persisting patellar maltracking following surgical realignment often remains unseen. The aim of this study was to analyze the effects of realignment procedures on patellofemoral kinematics in patients with patellofemoral instability (PFI) and patellofemoral maltracking (PM) by using dynamic magnetic resonance imaging (MRI). Patients planned for surgical patellar realignment due to PFI and a clinically and radiologically apparent PM between December 2019 and May 2022 were included. Patients without PM, limited range of motion, joint effusion, or concomitant injuries were excluded. Dynamic mediolateral translation (dMPT) and patella tilt (dPT) were measured preoperatively and three months postoperatively. In 24 patients (7 men, 17 women; mean age 23.0 years), 10 tibial tubercle transfers, 5 soft tissue patella tendon transfers, 6 trochleoplasties, 3 lateral lengthenings, 1 varizating distal femoral osteotomy (DFO), and 1 torsional DFO were performed. At final follow-up, dMPT (from 10.95 ± 5.93 mm to 4.89 ± 0.40 mm, p < 0.001) and dPT (from 14.50° ± 10.33° to 8.44° ± 7.46°, p = 0.026) were significantly improved. All static radiological parameters were corrected to physiological values. Surgical patellar realignment contributed to the significant improvement of patellofemoral kinematics, with an approximation to normal values. The postoperative application of dynamic MRI allowed for a quantification of the performed correction, allowing for a postoperative control of success.

(1) Background: In treating medial unicompartmental gonarthrosis, medial open wedge high tibial osteotomy (mOWHTO) reduces pain and is intended to delay a possible indication for joint replacement by relieving the affected compartment. This study aimed to investigate the influence of the osteotomy height with different hinge points in HTO in genu varum on the leg axis. (2) Methods: Fifty-five patients with varus lower leg alignment obtained full-weight bearing long-leg radiographs were analyzed. Different simulations were performed: Osteotomy height was selected at 3 and 4 cm distal to the tibial articular surface, and the hinge points were selected at 0.5 cm, 1 cm, and 1.5 cm medial to the fibular head, respectively. The target of each correction was 55% of the tibial plateau measured from the medial. Then, the width of the opening wedge was measured. Intraobserver and interobserver reliability were calculated. (3) Results: Statistically significant differences in wedge width were seen at an osteotomy height of 3 cm below the tibial plateau when the distance of the hinge from the fibular head was 0.5 cm to 1.5 cm (3 cm and 0.5 cm: 8.9 +/− 3.88 vs. 3 cm and 1.5 cm: 11.6 +/− 4.39 p = 0.012). Statistically significant differences were also found concerning the wedge width between the distances 0.5 to 1.5 cm from the fibular head at the osteotomy height of 4 cm below the tibial plateau. (4 cm and 0.5 cm: 9.0 +/− 3.76 vs. 4 cm and 1.5 cm: 11.4 +/− 4.27 p = 0.026). (4) Conclusion: A change of the lateral hinge position of 1 cm results in a change in wedge width of approximately 2 mm. If hinge positions are chosen differently in preoperative planning and intraoperatively, the result can lead to over- or under-correction.

Appendicular soft tissue lymphoma (ASTL) is rare and is frequently misinterpreted as soft tissue sarcoma (STS). Studies investigating magnet resonance imaging (MRI) characteristics of ASTL are scarce and showed heterogenous investigation criteria and results. The purpose of this study was to systematically review clinical presentations and MRI characteristics of ASTL as described in the current literature. For that purpose, we performed a systematic literature review in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Patient demographics, clinical presentation and MRI imaging characteristics of ASTL were investigated, resulting in a total of nine included studies reporting a total of 77 patients. Signal intensity of lymphoma compared to muscle tissue was mostly described as isointense (53%) or slightly hyperintense (39%) in T1-weighted images and always as hyperintense in proton-and T2-weighted images. Multicompartmental involvement was reported in 59% of cases and subcutaneous stranding in 74%. Long segmental involvement was present in 80% of investigated cases. Involvement of neurovascular structures was reported in 41% of cases and the presence of traversing vessels in 83% of patients. The presence of these findings should lead to the inclusion of ASTL in the differential diagnosis of soft tissue masses.

(1) The malposition of the femoral tunnel in medial patellofemoral ligament (MPFL) reconstruction can lead to length changes in the MPFL graft, and an increase in medial peak pressure in the patellofemoral joint. It is the cause of 36% of all MPFL revisions. According to Schöttle et al., the creation of the drill canal should be performed in a strictly lateral radiograph. In this study, it was hypothesized that positioning the image receptor to the knee during intraoperative fluoroscopy would lead to a relevant mispositioning of the femoral tunnel, despite an always adjusted true-lateral view. (2) A total of 10 distal femurs were created from 10 knee CT scans using a 3D printer. First, true-lateral fluoroscopies were taken from lateral to medial at a 25 cm (LM25) distance from the image receptor, then from medial to lateral at a 5 cm (ML5) distance. Using the method from Schöttle, the femoral origin of the MPFL was determined when the femur was positioned distally, proximally, superiorly, and inferiorly to the image receptor. (3) The comparison of the selected MPFL insertion points according to Schöttle et al. revealed that the initial determination of the point in the ML5 view resulted in a distal and posterior shift of the point by 5.3 mm ± 1.2 mm when the point was checked in the LM25 view. In the opposite case, when the MPFL insertion was initially determined in the LM25 view and then redetermined in the ML5 view, there was a shift of 4.8 mm ± 2.2 mm anteriorly and proximally. The further positioning of the femur (distal, proximal, superior, and inferior) showed no relevant influence. (4) For fluoroscopic identification of the femoral MPFL, according to Schöttle et al., attention should be paid to the position of the fluoroscopy in addition to a true-lateral view.

Intramuscular myxomas (IMMs) are benign tumors. Evidence regarding diagnostic and therapeutic pathways is rare, and guidelines do not exist due to their low incidence. The aim of this study was a retrospective analysis at a university cancer center and the interdisciplinary re-evaluation of the individual diagnostic and therapeutic procedures. Overall, 38 patients were included in the study. IMMs occurred mostly in middle-aged women. At the time of first consultation, 57.9% had few symptoms or were asymptomatic. In 92.1% of the cases, the tumor was localized in the extremities. The lower extremity was affected in 73.7%. The average size of IMMs was 5.0 cm. The proximally located tumors in the gluteus, thighs, and upper arms were significantly larger (p = 0.02) than the distally-located tumors in the forearms and lower legs. An MRI was performed in 97.4%. Based on imaging, an IMM was suspected in 5.6% by radiologists and in 54.1% by musculoskeletal surgeons. An incision biopsy was performed in 68.4% and led in 100.0% to the right histopathological diagnosis. In total, 89.5% of IMMs were resected. Postoperative complications requiring revision occurred in 8.8%. Recurrences or degenerations of IMMs were not reported in any of these cases.

Lipomatous tumors are among the most common soft tissue tumors (STTs). Magnetic resonance imaging (MRI) is a state-of-the-art diagnostic tool used to differentiate and characterize STTs. Radiological misjudgment can lead to incorrect treatment. This was a single-center retrospective study. Two hundred and forty lipomatous tumors were included. MRI diagnoses were categorized as benign, intermediate, or malignant and were compared with histological diagnoses. Tumor volumes were measured by MRI and from surgical specimens. The tumor was correctly categorized 73.3% of the time. A total of 21.7% of tumors were categorized as more malignant in MRI reports than they were by histology, and vice versa for 5.0% of tumors. Volume measured by MRI was not different from actual tumor size in pathology. Atypical lipomatous tumors (ALTs) and liposarcomas (LPSs) were larger when compared with lipomata and occurred in older patients. Based on the MRI-suspected tumor entity, surgical treatment can be planned. Large lipomatous tumors in elderly patients are more likely to be ALTs. However, a safe threshold size or volume for ALTs cannot be determined.

Background: Impaired fracture healing represents an ongoing clinical challenge, as treatment options remain limited. Calcitonin gene-related peptide (CGRP), a neuropeptide targeted by emerging anti-migraine drugs, is also expressed in sensory nerve fibres innervating bone tissue. Method: Bone healing following a femoral osteotomy stabilized with an external fixator was analysed over 21 days in αCGRP-deficient and WT mice. Bone regeneration was evaluated by serum analysis, µCT analysis, histomorphometry and genome-wide expression analysis. Bone-marrow-derived osteoblasts and osteoclasts, as well as the CGRP antagonist olcegepant were employed for mechanistic studies. Findings: WT mice with a femoral fracture display increased CGRP serum levels. αCGRP mRNA expression after skeletal injury is exclusively induced in callus tissue, but not in other organs. On protein level, CGRP and its receptor, calcitonin receptor-like receptor (CRLR) complexing with RAMP1, are differentially expressed in the callus during bone regeneration. On the other hand, αCGRP-deficient mice display profoundly impaired bone regeneration characterised by a striking reduction in the number of bone-forming osteoblasts and a high rate of incomplete callus bridging and non-union. As assessed by genome-wide expression analysis, CGRP induces the expression of specific genes linked to ossification, bone remodeling and adipogenesis. This suggests that CGRP receptor-dependent PPARγ signaling plays a central role in fracture healing. Interpretation: This study demonstrates an essential role of αCGRP in orchestrating callus formation and identifies CGRP receptor agonism as a potential approach to stimulate bone regeneration. Moreover, as novel agents blocking CGRP or its receptor CRLR are currently introduced clinically for the treatment of migraine disorders, their potential negative impact on bone regeneration warrants clinical investigation. Funding: This work was funded by grants from the Else-Kröner-Fresenius-Stiftung (EKFS), the Deutsche Forschungsgemeinschaft (DFG), and the Berlin Institute of Health (BIH).

Introduction. Osteogenesis imperfecta (OI) is the term for a heterogenic group of conatal diseases that affect the bone formation. Eight different OI types are known. Patients with types III and IV frequently suffer from fractures without adequate trauma. The literature gives plenty advice for fracture treatment in pediatric OI patients, but there is less for adults, and no recommendations can be found for geriatric OI patients. Case Presentation. We report on an 83-year-old male who suffered from OI type IV. He was able to walk with an individually adapted gait orthosis. In an accident, the patient sustained a distal, multifragment, femoral shaft fracture. The fracture was openly reduced and fixated with a retrograde inserted elastic stable intramedullary nail (ESIN). Three months later, the patient was capable of walking without crutches. Due to another accident, he sustained a peri-implant refracture without failure of the ESIN. We immobilized the leg, and it achieved bony healing without reosteosynthesis. Eleven weeks later, he was again able to mobilize himself with full weight bearing. Discussion. We present a unique case of osteosynthesis in a distal, multifragment, femoral shaft fracture in a geriatric OI patient. No recommendations for the treatment of mature patients with OI can be found in the literature. We present our treatment concept and technique of osteosynthesis with an ESIN. Despite another accident with a peri-implant refracture, sufficient bony healing occurred, which allowed the patient to freely mobilize himself again.

Abstract Background To systematically review all available studies of operatively treated proximal tibia fractures and to report the incidence of superficial or deep infection and subsequent outcomes. Methods A systematic review of the literature in Medline, Cochrane, Embase and GoogleScholar was conducted to identify studies with cohorts of patients with infection after surgical treatment of proximal tibia fractures. Studies were included according to predefined inclusion and exclusion criteria. The studies were analysed for methodological deficiencies and quality of outcome reporting based on the Level of Evidence (LOE) and Coleman Methodology Scoring (CMS.) Results In total 32 studies were included. There was heterogeneity between the studies, in terms of subject of the studies, outcome criteria, fracture type and classification, surgical techniques and length of follow-up. Therefore, no meta-analysis could be performed. The average CMS was 54.2 (range 36–75). The included studies were 25 case series (LOE IV), 6 were prospective cohort studies (LOE III) and one was a prospective randomized trial (LOE I). 203 (12.3%, range: 2.6–45.0%) infections occurred in the overall population (n = 2063). Those were divided into 129 deep infections and 74 superficial infections. Revision due to infection was reported in 29 studies, microbiological results in 6, respectively. 72 (55,8%) of 129 cases reporting outcome after deep infection had an unsatisfactory outcome with substantial limitations of the affected joint and leg. Conclusions Postoperative infections are a challenge, sometimes requiring several revisions and often with a worse outcome. Further studies with structured study protocols should be performed for a better understanding of risk factors to improve treatment outcomes.

Despite significant advances in surgical techniques, treatment options for impaired bone healing are still limited. Inadequate bone regeneration is not only associated with pain, prolonged immobilization and often multiple revision surgeries, but also with high socioeconomic costs, underlining the importance of a detailed understanding of the bone healing process. In this regard, we previously showed that mice lacking the calcitonin receptor (CTR) display increased bone formation mediated through the increased osteoclastic secretion of sphingosine-1-phosphate (S1P), an osteoanabolic molecule promoting osteoblast function. Although strong evidence is now available for the crucial role of osteoclast-to-osteoblast coupling in normal bone hemostasis, the relevance of this paracrine crosstalk during bone regeneration is unknown. Therefore, our study was designed to test whether increased osteoclast-to-osteoblast coupling, as observed in CTR-deficient mice, may positively affect bone repair. In a standardized femoral osteotomy model, global CTR-deficient mice displayed no alteration in radiologic callus parameters. Likewise, static histomorphometry demonstrated moderate impairment of callus microstructure and normal osseous bridging of osteotomy ends. In conclusion, bone regeneration is not accelerated in CTR-deficient mice, and contrary to its osteoanabolic action in normal bone turnover, osteoclast-to-osteoblast coupling specifically involving the CTR-S1P axis, may only be of minor relevance during bone healing.

Osteoid osteoma (OO) is a benign bone tumor producing non-mineralized bone matrix (i.e., osteoid). While peritumoral edema is commonly found in OO, extensive bone marrow edema has been reported less frequently. Furthermore, the micro-morphological characteristics of the nidus and its central calcification remain unclear. In this study, a consecutive series of four patients suffering from extensive bone marrow edema triggered by intra-articular osteoid osteoma underwent clinical examination, magnetic resonance imaging (MRI) and computed tomography (CT) as well as dual-energy X-ray absorptiometry (DXA) and laboratory bone turnover analyses. The obtained resection specimens were processed by undecalcified histology and were subsequently analyzed by light microscopy and quantitative backscattered electron imaging (qBEI). We report an entity of intra-articular osteoid osteoma in the knee and foot, in which an extensive and persistent bone marrow edema syndrome masked the correct diagnosis. While metabolic bone diseases were excluded in all cases, the reassessment of the patients’ clinical history including pain characteristics (nocturnal, aspirin sensitivity) led us to perform additional CT, where the tumor was diagnosed. The micro-morphological analysis of the OO biopsies revealed that the nidus was surrounded by hyperosteoidosis, while central mineralization was detected in all cases. This mineralized area showed a significantly higher mineralization heterogeneity than the surrounding trabecular bone and more disorganized collagen fibers detected by qBEI and polarized light microscopy, respectively. Taken together, our results indicate that osteoid osteoma should be considered when persistent and extensive, peri-articular bone marrow edema is diagnosed. The central calcification that is found inside the nidus in conventional imaging was mirrored by bone matrix with a heterogeneous mineralization pattern. Keywords: Osteoid osteoma, Bone marrow edema, Joint pain, Bone tumor, MRI, qBEI

Posterolateral impression fractures of the tibial plateau are common, and open reduction and fixation can be demanding, including exposure of the peroneal nerve. Based on a patient example, the surgical technique of an arthroscopic controlled closed reduction and percutaneous screw fixation of a posterolateral tibia plateau impressed fracture is described. A patient sustained a posterolateral impression currently described as an “apple bite” fracture of the tibial plateau. The surgical technique includes standard arthroscopic portals and posteromedial and (transseptal) posterolateral portals. The posterolateral tibial plateau is visualized by incision of popliteomeniscal fibers, retraction of the popliteus tendon, and exposure of the posterolateral plateau. The impression area is marked with a K-wire using an anterior cruciate ligament target device. A cannulated ram is placed over the K-wire. The fracture is lifted under arthroscopic guidance and can be supported with allograft bone chips. To stabilize the reduction, 3 K-wires are positioned from anterior to posterior, and 3 cannulated screws are inserted directly under the joint surface to support the fractured area. In comparison with open surgical techniques, this procedure is exclusively performed under arthroscopic control and enables an anatomic reduction and fixation of the posterolateral tibial plateau.

Injuries of the posterolateral corner (PLC) of the knee lead to chronic lateral and external rotational instability. Successful treatment of PLC injuries requires an understanding of the complex anatomy and biomechanics of the PLC. Several open PLC reconstruction techniques have been published. It is understood that anatomic reconstruction is superior to extra-anatomic techniques, leading to better clinical results. An open, anatomic, fibula-based technique for reconstruction to address lateral and rotational instability has been described. However, when an open technique is used, surgeon and patient are faced with disadvantages, such as soft tissue damage or exposure of vulnerable structures. Few arthroscopic techniques for tibia- or fibula-based reconstruction of rotational posterolateral instability have been described. A complete arthroscopic stabilization of the combined lateral and posterolateral rotational instability of the knee has not yet been described. We therefore present the first all-arthroscopic technique for complete PLC reconstruction, based on an open technique described previously. All relevant landmarks of the PLC can be arthroscopically visualized in detail, allowing safe and effective treatment of PLC injuries.

PURPOSE:The purpose of this study was to compare the biomechanical properties of an all-suture anchor to a conventional anchor used commonly in rotator cuff repairs. Furthermore, the biomechanical influence of various implantation angles was evaluated in both anchor types in a human cadaveric model. METHODS:30 humeri were allocated into three groups with a similar bone density. The two different anchor types were inserted at a predefined angle of 45°, 90° or 110°. Biomechanical testing included an initial preload of 20N followed by a cyclic protocol with a stepwise increasing force of 0,05N for each cycle at a rate of 1Hz until system failure. Number of cycles, maximum load to failure, stiffness, displacement and failure mode were determined. RESULTS:27 anchors failed by pullout. There was no significant difference between the conventional and the all-suture anchor regarding mean pullout strength. No considerable discrepancy in stiffness or displacement could be perceived. Comparing the three implantation angles no significant difference could be observed for the all-suture or the conventional anchor. CONCLUSION:All-suture anchors show similar biomechanical properties to conventional screw shaped anchors in an unlimited cyclic model. The exact insertion angle is not a significant predictor of failure.

Bone tissue in vertebrates is essential to performing movements, to protecting internal organs and to regulating calcium homeostasis. Moreover, bone has also been suggested to contribute to whole-body physiology as an endocrine organ, affecting male fertility; brain development and cognition; and glucose metabolism. A main determinant of bone quality is the constant remodeling carried out by osteoblasts and osteoclasts, a process consuming vast amounts of energy. In turn, clinical conditions associated with impaired glucose metabolism, including type I and type II diabetes and anorexia nervosa, are associated with impaired bone turnover. As osteoblasts are required for collagen synthesis and matrix mineralization, they represent one of the most important targets for pharmacological augmentation of bone mass. To fulfill their function, osteoblasts primarily utilize glucose through aerobic glycolysis, a process which is regulated by various molecular switches and generates adenosine triphosphate rapidly. In this regard, researchers have been investigating the complex processes of energy utilization in osteoblasts in recent years, not only to improve bone turnover in metabolic disease, but also to identify novel treatment options for primary bone diseases. This review focuses on the metabolism of glucose in osteoblasts in physiological and pathophysiological conditions.

Soft-tissue sarcomas (STS) are a rare subtype of soft-tissue mass and are frequently misinterpreted as benign lesions. Magnetic resonance imaging (MRI) is the primary recommended type of diagnostics. To assess the quality of primary radiology reports, we investigated whether recommended MRI report elements were included in compliance with European Society of Musculoskeletal Radiology (ESSR) guidelines. A total of 1107 patients were evaluated retrospectively, and 126 radiological reports on patients with malignant STS were assessed for ESSR quality criteria. One or more required sequences or planes were missing in 67% of the reports. In all 126 cases, the report recognized the mass as anomalous (100%). Sixty-eight percent of the reports mentioned signs of malignancy. The majority of reports (n = 109, 87%) articulated a suspected diagnosis, 32 of which showed a mismatch with the final diagnosis (25%). Thirty-two percent of the reports had a misinterpretation of the masses as benign. Benign misinterpretations were more common in masses smaller than 5 cm (65% vs. 27%). Thirty percent of the reports suggested tissue biopsy and 6% recommended referral to a sarcoma center. MRI reports showed frequent deviations from ESSR guidelines, and protocol guidelines were not routinely met. Deviations from standard protocol and reporting guidelines could put patients at risk for inadequate therapy.

Despite modern surgical trauma care, bleeding contributes to one-third of trauma-related death. A significant improvement was obtained through the introduction of tranexamic acid (TXA), which today is widely used in emergency and elective orthopedic surgery to control bleeding. However, concerns remain regarding potential adverse effects on bone turnover and regeneration. Therefore, we employed standardized cell culture systems including primary osteoblasts, osteoclasts, and macrophages to evaluate potential effects of TXA on murine bone cells. While osteoblasts derived from calvarial digestion were not affected, TXA increased cell proliferation and matrix mineralization in bone marrow-derived osteoblasts. Short-term TXA treatment (6 h) failed to alter the expression of osteoblast markers; however, long-term TXA stimulation (10 days) was associated with the increased expression of genes involved in osteoblast differentiation and extracellular matrix synthesis. Similarly, whereas short-term TXA treatment did not affect gene expression in terminally differentiated osteoclasts, long-term TXA stimulation resulted in the potent inhibition of osteoclastogenesis. Finally, in bone marrow-derived macrophages activated with LPS, simultaneous TXA treatment led to a reduced expression of inflammatory cytokines and chemokines. Collectively, our study demonstrates a differential action of TXA on bone cells including osteoanabolic, anti-resorptive, and anti-inflammatory effects in vitro which suggests novel treatment applications.

Notch1-4 receptors and their signaling pathways are expressed in almost all organ systems and play a pivotal role in cell fate decision by coordinating cell proliferation, differentiation and apoptosis. Differential expression and activation of Notch signaling pathways has been observed in a variety of organs and tissues under physiological and pathological conditions. Bone tissue represents a dynamic system, which is constantly remodeled throughout life. In bone, Notch receptors have been shown to control remodeling and regeneration. Numerous functions have been assigned to Notch receptors and ligands, including osteoblast differentiation and matrix mineralization, osteoclast recruitment and cell fusion and osteoblast/osteoclast progenitor cell proliferation. The expression and function of Notch1-4 in the skeleton are distinct and closely depend on the temporal expression at different differentiation stages. This review addresses the current knowledge on Notch signaling in adult bone with emphasis on metabolism, bone regeneration and degenerative skeletal disorders, as well as congenital disorders associated with mutant Notch genes. Moreover, the crosstalk between Notch signaling and other important pathways involved in bone turnover, including Wnt/β-catenin, BMP and RANKL/OPG, are outlined.

As brain and bone disorders represent major health issues worldwide, substantial clinical investigations demonstrated a bidirectional crosstalk on several levels, mechanistically linking both apparently unrelated organs. While multiple stress, mood and neurodegenerative brain disorders are associated with osteoporosis, rare genetic skeletal diseases display impaired brain development and function. Along with brain and bone pathologies, particularly trauma events highlight the strong interaction of both organs. This review summarizes clinical and experimental observations reported for the crosstalk of brain and bone, followed by a detailed overview of their molecular bases. While brain-derived molecules affecting bone include central regulators, transmitters of the sympathetic, parasympathetic and sensory nervous system, bone-derived mediators altering brain function are released from bone cells and the bone marrow. Although the main pathways of the brain-bone crosstalk remain ‘efferent’, signaling from brain to bone, this review emphasizes the emergence of bone as a crucial ‘afferent’ regulator of cerebral development, function and pathophysiology. Therefore, unraveling the physiological and pathological bases of brain-bone interactions revealed promising pharmacologic targets and novel treatment strategies promoting concurrent brain and bone recovery.

Bone regeneration represents a complex process, of which basic biologic principles have been evolutionarily conserved over a broad range of different species. Bone represents one of few tissues that can heal without forming a fibrous scar and, as such, resembles a unique form of tissue regeneration. Despite a tremendous improvement in surgical techniques in the past decades, impaired bone regeneration including non-unions still affect a significant number of patients with fractures. As impaired bone regeneration is associated with high socio-economic implications, it is an essential clinical need to gain a full understanding of the pathophysiology and identify novel treatment approaches. This review focuses on the clinical implications of impaired bone regeneration, including currently available treatment options. Moreover, recent advances in the understanding of fracture healing are discussed, which have resulted in the identification and development of novel therapeutic approaches for affected patients.