[Non-unions of the upper extremities]. / Pseudarthrosen der oberen Extremität.

The diagnosis and treatment of non-unions still represents an interdisciplinary challenge. Therefore, prevention, early detection and specific treatment are of great importance. Non-unions of the upper extremities, although less common than that of the lower extremities, requires special attention for successful treatment due to the central role of the shoulder girdle and arm in day to day activities. Successful treatment of non-unions requires a comprehensive evaluation of the patient's medical history, a thorough clinical examination and in particular radiological imaging. In order to effectively treat the pseudarthrosis it is crucial to distinguish between pseudarthroses that are suspected to be due to infections and those that are not. This article presents a treatment algorithm for managing both pseudarthrosis due to infection and pseudarthrosis without infection in the upper extremities.

Sildenafil delays bone remodeling of fractured femora in aged mice by reducing the number and activity of osteoclasts within the callus tissue.

The elderly exhibit a reduced healing capacity after fracture, which is often associated with delayed or failed bone healing. This is due to a plethora of factors, such as an impaired bone vascular system and delayed angiogenesis. The phosphodiesterase-5 (PDE-5) inhibitor sildenafil exerts pro-angiogenic and pro-osteogenic effects. Hence, we herein investigated in aged mice whether sildenafil can improve fracture healing. For this purpose, 40 aged CD-1 mice (16-18 months) were daily treated with 5 mg/kg body weight sildenafil (n = 20) or vehicle (control, n = 20) by oral gavage. The callus tissue of their femora was analyzed at 2 and 5 weeks after fracture by X-ray, biomechanics, micro-computed tomography (µCT), histology, immunohistochemistry as well as Western blotting. These analyses revealed a significantly increased bone volume and higher ratio of callus to femoral bone diameter in sildenafil-treated mice at 5 weeks after fracture when compared to controls. This was associated with a reduced number and activity of osteoclasts at 2 weeks after fracture, most likely caused by an increased expression of osteoprotegerin (OPG). Taken together, these findings indicate that sildenafil does not improve fracture healing in the elderly but delays the process of bone remodeling most likely by reducing the number and activity of osteoclasts within the callus tissue.

[Nonunions after intertrochanteric and subtrochanteric femoral fractures]. / Pseudarthrosen nach per- und subtrochantären Femurfrakturen.

INTRODUCTION: The overall frequency of proximal femoral fractures means that we are repeatedly confronted with failed healing and implant failure, despite a relatively low nonunion rate especially in intertrochanteric fractures (< 5%). The aim of this paper is to present our approach to treating these nonunions of the proximal femur and discuss the treatment results. MATERIAL AND METHODS: Between 2009 and 2023, patients with nonunion of the proximal femur were retrospectively identified and analyzed. Age, gender, time to revision, the Weber-Cech classification of pseudarthrosis and radiographic imaging before and after revision were analyzed. RESULTS: A total of 66 patients were analyzed. The mean age was 58 years (range 25-88 years). The overall healing rate was 88% with a mean consolidation time of 8 months (range 2-29 months). The main osteosynthesis procedures were plate osteosynthesis (n = 45, of which 44 were blade plates), and nail replacement (n = 12). Other procedures included augmentative plate osteosyntheses (n = 4), isolated cancellous bone graft (n = 2), nail dynamization (n = 2), and the use of a dynamic hip screw (n = 1). DISCUSSION: The analysis of our treatment data as well as the current literature, revealed a trend towards intramedullary revision procedures. Implants that can be used to correct the CCD angle, such as the blade plate, remain a predictable option to achieve correction, especially in nonunions with an increased degree of varus. Particularly in the subtrochanteric region, fractures can also be treated in a targeted manner by a combination of mechanical and biological methods with a reamed nail change to a larger caliber implant.

"Fall Risk Scoring" in Outpatient Gait Analysis: Validation of a New Fall Risk Assessment for Nursing Home Residents. / "Fall Risk Scoring" in der ambulanten Ganganalyse: Validierung eines neuen Sturzrisikoassessments bei Heimbewohnern.

Falls in senior home residents are common. Individual preventive training can lower the fall risk. To detect the need for training, a systematic assessment of the individual fall risk is needed. The aim of this study was thus to assess whether a fall risk score based on free field insole measurements can distinguish between an at-risk group of senior home residents and a healthy young control group. A published fall risk score was used in senior home residents over the age of 75 and a young (< 40 years) control group to determine the individual fall risk. In addition, the fall events over 12 months were assessed. Statistical analysis including ROC analysis was performed to determine the ability of the score to detect participants at heightened fall risk. In total, 18 nursing home residents and 9 young control participants were included. Of the nursing home residents, 15 had at least one fall, with a total of 37 falls recorded over 12 months. In the control group, no falls were recorded. The fall risk score was significantly different between nursing home residents and the control group (9.2 + 3.2 vs. 5.7 ± 2.2). Furthermore, the score significantly differentiated fallers from non-fallers (10.3 ± 1.8 vs. 5.2 ± 2.5), with a cut-off > 7.5 (AUC: 0.95) and a sensitivity of 86.7% (specificity 83.3%). The fall risk score is able to detect the difference between senior nursing home residents and young, healthy controls, as well as between fallers and non-fallers. Its main proof of concept is demonstrated, as based on movement data outside special gait labs, and it can simplify the risk of fall determination in geriatric nursing home residents and can now be used in further, prospective studies.

Sildenafil, a phosphodiesterase-5 inhibitor, stimulates angiogenesis and bone regeneration in an atrophic non-union model in mice.

Non-union formation represents a major complication in trauma and orthopedic surgery. The phosphodiesterase-5 (PDE-5) inhibitor sildenafil has been shown to exert pro-angiogenic and pro-osteogenic effects in vitro and in vivo. Therefore, the aim of the present study was to analyze the impact of sildenafil in an atrophic non-union model in mice. After creation of a 1.8 mm segmental defect, mice femora were stabilized by pin-clip fixation. Bone regeneration was analyzed by means of X-ray, biomechanics, photoacoustic and micro-computed tomography (µCT) imaging as well as histological, immunohistochemical and Western blot analyses at 2, 5 and 10 weeks after surgery. The animals were treated daily with either 5 mg/kg body weight sildenafil (n = 35) or saline (control; n = 35) per os. Bone formation was markedly improved in defects of sildenafil-treated mice when compared to controls. This was associated with a higher bending stiffness as well as an increased number of CD31-positive microvessels and a higher oxygen saturation within the callus tissue. Moreover, the bone defects of sildenafil-treated animals contained more tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD68-positive macrophages and exhibited a higher expression of the pro-angiogenic and pro-osteogenic markers cysteine rich protein (CYR)61 and vascular endothelial growth factor (VEGF) when compared to controls. These findings demonstrate that sildenafil acts as a potent stimulator of angiogenesis and bone regeneration in atrophic non-unions.

Increased Levels of BAMBI Inhibit Canonical TGF-ß Signaling in Chronic Wound Tissues.

Chronic wounds affect more than 2% of the population worldwide, with a significant burden on affected individuals, healthcare systems, and societies. A key regulator of the entire wound healing cascade is transforming growth factor beta (TGF-ß), which regulates not only inflammation and extracellular matrix formation but also revascularization. This present work aimed at characterizing wound tissues obtained from acute and chronic wounds regarding angiogenesis, inflammation, as well as ECM formation and degradation, to identify common disturbances in the healing process. Serum and wound tissues from 38 patients (N = 20 acute and N = 18 chronic wounds) were analyzed. The patients' sera suggested a shift from VEGF/VEGFR to ANGPT/TIE2 signaling in the chronic wounds. However, this shift was not confirmed in the wound tissues. Instead, the chronic wound tissues showed increased levels of MMP9, a known activator of TGF-ß. However, regulation of TGF-ß target genes, such as CTGF, COL1A1, or IL-6, was absent in the chronic wounds. In wound tissues, all three TGF-ß isoforms were expressed with increased levels of TGF-ß1 and TGF-ß3 and a reporter assay confirmed that the expressed TGF-ß was activated. However, Western blots and immunostaining showed decreased canonical TGF-ß signaling in the respective chronic wound tissues, suggesting the presence of a TGF-ß inhibitor. As a potential regulatory mechanism, the TGF-ß proteome profiler array suggested elevated levels of the TGF-ß pseudo-receptor BAMBI. Also, tissue expression of BAMBI was significantly increased not only in chronic wounds (10.6-fold) but also in acute wounds that had become chronic (9.5-fold). In summary, our data indicate a possible regulatory role of BAMBI in the development of chronic wounds. The available few in vivo studies support our findings by postulating a therapeutic potential of BAMBI for controlling scar formation.

Diclofenac, a NSAID, delays fracture healing in aged mice.

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, belong to the most prescribed analgesic medication after traumatic injuries. However, there is accumulating evidence that NSAIDs impair fracture healing. Because bone regeneration in aged patients is subject to significant changes in cell differentiation and proliferation as well as a markedly altered pharmacological action of drugs, we herein analyzed the effects of diclofenac on bone healing in aged mice using a stable closed femoral facture model. Thirty-three mice (male n = 14, female n = 19) received a daily intraperitoneal injection of diclofenac (5 mg/kg body weight). Vehicle-treated mice (n = 29; male n = 13, female n = 16) served as controls. Fractured mice femora were analyzed by means of X-ray, biomechanics, micro computed tomography (µCT), histology and Western blotting. Biomechanical analyses revealed a significantly reduced bending stiffness in diclofenac-treated animals at 5 weeks after fracture when compared to vehicle-treated controls. Moreover, the callus tissue in diclofenac-treated aged animals exhibited a significantly reduced amount of bone tissue and higher amounts of fibrous tissue. Further histological analyses demonstrated less lamellar bone after diclofenac treatment, indicating a delay in callus remodeling. This was associated with a decreased number of osteoclasts and an increased expression of osteoprotegerin (OPG) during the early phase of fracture healing. These findings indicate that diclofenac delays fracture healing in aged mice by affecting osteogenic growth factor expression and bone formation as well as osteoclast activity and callus remodeling.

Radiographic, Biomechanical and Histological Characterization of Femoral Fracture Healing in Aged CD-1 Mice.

With a gradually increasing elderly population, the treatment of geriatric patients represents a major challenge for trauma and reconstructive surgery. Although, it is well established that aging affects bone metabolism, it is still controversial if aging impairs bone healing. Accordingly, we investigated fracture healing in young adult (3-4 months) and aged (16-18 months) CD-1 mice using a stable closed femoral fracture model. Bone healing was analyzed by radiographic, biomechanical and histological analysis at 1, 2, 3, 4 and 5 weeks after fracture. Our results demonstrated an increased callus diameter to femoral diameter ratio in aged animals at later time points of fracture healing when compared to young adult mice. Moreover, our biomechanical analysis revealed a significantly decreased bending stiffness at 3 and 4 weeks after fracture in aged animals. In contrast, at 5 weeks after fracture, the analysis showed no significant difference in bending stiffness between the two study groups. Additional histological analysis showed a delayed endochondral ossification in aged animals as well as a higher amounts of fibrous tissue at early healing time points. These findings indicate a delayed process of callus remodeling in aged CD-1 mice, resulting in a delayed fracture healing when compared to young adult animals. However, the overall healing capacity of the fractured femora was not affected by aging.

Photoacoustic imaging for the study of oxygen saturation and total hemoglobin in bone healing and non-union formation.

Non-union formation represents a major complication in trauma surgery. Adequate vascularization has been recognized as vital for bone healing. However, the role of vascularization in the pathophysiology of non-union formation remains elusive. This is due to difficulties in studying bone microcirculation in vivo. Therefore, we herein studied in a murine osteotomy model whether photoacoustic imaging may be used to analyze vascularization in bone healing and non-union formation. We found that oxygen saturation within the callus tissue is significantly lower in non-unions compared to unions and further declines over time. Moreover, the amount of total hemoglobin (HbT) within the callus tissue was markedly reduced in non-unions. Correlation analyses showed a strong positive correlation between microvessel density and HbT, indicating that photoacoustically determined HbT is a valid parameter to assess vascularization during bone healing. In summary, photoacoustic imaging is a promising approach to study vascular function and tissue oxygenation in bone regeneration.

[Cement augmentation in pelvic ring fractures]. / Zementaugmentation bei Beckenringfrakturen.

Cement augmentation of sacroiliac (SI) screws in the posterior pelvic ring has been shown to provide greater biomechanical stability in cadaveric studies. Pelvic ring fractures are relatively rare compared to the total number of fractures. Nevertheless, the 1­year mortality rate of up to 27% is very high, especially for geriatric pelvic ring fractures and is also largely associated with reduced mobility due to the fracture. The primary goal of treatment is therefore the restoration of patient mobility. This requires the achievement of sufficient stability of the pelvic ring. As osteoporosis is often a causative factor for the pelvic ring fracture, a more stable anchoring of the implants in the osteoporotic bone can be achieved by cement augmentation. This article presents the possibilities of cement augmentation of the pelvic ring and describes the technique of cement-augmented SI screws.

[Artificial intelligence and novel approaches for treatment of non-union in bone : From established standard methods in medicine up to novel fields of research]. / Künstliche Intelligenz und Ausblick auf Anwendungsfelder in der Pseudarthrosentherapie : Von etablierten Standardmethoden in der Medizin hin zu neuen Forschungsfeldern.

Methods of artificial intelligence (AI) have found applications in many fields of medicine within the last few years. Some disciplines already use these methods regularly within their clinical routine. However, the fields of application are wide and there are still many opportunities to apply these new AI concepts. This review article gives an insight into the history of AI and defines the special terms and fields, such as machine learning (ML), neural networks and deep learning. The classical steps in developing AI models are demonstrated here, as well as the iteration of data rectification and preparation, the training of a model and subsequent validation before transfer into a clinical setting are explained. Currently, musculoskeletal disciplines implement methods of ML and also neural networks, e.g. for identification of fractures or for classifications. Also, predictive models based on risk factor analysis for prevention of complications are being initiated. As non-union in bone is a rare but very complex disease with dramatic socioeconomic impact for the healthcare system, many open questions arise which could be better understood by using methods of AI in the future. New fields of research applying AI models range from predictive models and cost analysis to personalized treatment strategies.

[Movement analysis and musculoskeletal simulation in non-union treatment-Experiences and first clinical results]. / Bewegungsanalyse und muskuloskeletale Simulation in der Pseudarthrosentherapie ­ Erfahrungen und erste klinische Ergebnisse.

BACKGROUND: The mechanical boundary conditions of the non-union and osteosynthetic construct are a key determinant of fracture healing after revision surgery. Aim of this study was to introduce a movement analysis and simulation workflow to determine the mechanical conditions during non-union healing in vivo. MATERIAL AND METHODS: On an individual case basis after non-union revision surgery we performed an accelerometry-based movement analysis. The results were then used as input for a musculoskeletal simulation of the non-union, osteosynthetic construct as well as adjacent joints mechanical boundary conditions. RESULTS: A total of 13 patients were analyzed with our new workflow. The introduced protocol allows an in vivo determination of the mechanical boundary conditions. On clinical follow-up all patients showed radiographic consolidation of the non-union. CONCLUSION: The introduced workflow allows a clinically applicable determination of the mechanical boundary conditions of fracture and non-union healing. Further studies can now determine the effect of the introduced technique for mechanically optimized postoperative aftercare regimes as well as biomechanically adapted surgical treatment.

Development of an ischemic fracture healing model in mice.

BACKGROUND AND PURPOSE: In fracture healing, ischemia caused by vascular injuries, chronic vascular diseases, and metabolic comorbidities is one of the major risk factors for delayed union and non-union formation. To gain novel insights into the molecular and cellular pathology of ischemic fracture healing, appropriate animal models are needed. Murine models are of particular interest, as they allow to study the molecular aspects of fracture healing due to the availability of both a large number of murine antibodies and gene-targeted animals. Thus, we present the development of an ischemic fracture healing model in mice. MATERIAL AND METHODS: After inducing a mild ischemia by double ligature of the deep femoral artery in CD-1 mice, the ipsilateral femur was fractured by a 3-point bending device and stabilized by screw osteosynthesis. In control animals, the femur was fractured and stabilized without the induction of ischemia. The femora were analyzed at 2 and 5 weeks after fracture healing by means of radiology, biomechanics, histology, and histomorphometry. RESULTS: The surgically induced ischemia delayed and impaired the process of fracture healing. This was indicated by a lower Goldberg score, decreased bending stiffness, and reduced bone callus formation in the ischemic animals when compared with the controls. INTERPRETATION: We introduce a novel ischemic femoral fracture healing model in mice, which is characterized by delayed bone healing. In future, the use of this model may allow both the elucidation of the molecular aspects of ischemic fracture healing and the study of novel treatment strategies.

[Atrophic sternum nonunion-Case report based on the nonunion scoring system]. / Atrophe Pseudarthrose des Sternums ­ ein Fallbericht orientiert am Non Union Scoring System.

Nonunions after median sternotomy are rare and usually respond well to surgical treatment. Recalcitrant nonunions despite surgical treatment require a comprehensive mechanical and biological treatment strategy to achieve an adequate functional result for the patient. We demonstrate the case of a 4-year recalcitrant atrophic nonunion. Through a surgical approach guided by the criteria of the nonunion scoring system (NUSS) successful healing was achieved. Our strategy as well as the treatment course are presented.

Establishment of a Reliable Model to Study the Failure of Fracture Healing in Aged Mice.

The failure of fracture healing represents a substantial clinical problem. Moreover, aged patients demonstrate an elevated risk for failed bone healing. However, murine models to study the failure of fracture healing are established only in young adult animals. Therefore, the aim of this study was to develop a reliable model to study failed fracture healing in aged mice. After creation of a 1.8-mm segmental defect and periosteal resection, femora of aged mice (18-20 months) and young adult control mice (3-4 months) were stabilized by pin-clip fixation. Segmental defects were analyzed by means of biomechanics, x-ray, and micro-computed tomography, as well as histomorphometric, immunohistochemical, and Western blot analysis. After 10 weeks, all animals showed a complete lack of osseous bridging, resulting in fracture healing failure. Segmental defects in aged mice revealed a reduced bone formation and vascularization when compared to young adult mice. This was associated with a decreased expression of bone formation markers. In addition, we detected a reduced number of tartrate-resistant acid phosphatase-positive osteoclasts and an elevated osteoprotegerin/receptor activator of NF-ĸB ligand ratio in aged animals, indicating a reduced osteoclast activity. Moreover, aged animals showed also an enhanced inflammatory response, characterized by an increased infiltration of macrophages within the callus tissue. Taken together, we herein report for the first time a reliable model to study fracture healing failure in aged mice. In the future, the use of this model enables us to study novel therapeutic strategies and molecular mechanics of failed fracture healing during aging.

Fractures of the femoral head: a narrative review.

Fractures of the femoral head are rare injuries, which typically occur after posterior hip dislocation.The Pipkin classification, developed in 1957, is the most commonly used classification scheme to date.The injury is mostly caused by high-energy trauma, such as motor vehicle accidents or falls from a significant height.Emergency treatment consists of urgent closed reduction of the hip joint, followed by non-operative or operative treatment of the femoral head fracture and any associated injuries.There is an ongoing controversy about the suitable surgical approach (anterior vs. posterior) for addressing fractures of the femoral head. Fracture location, degree of displacement, joint congruity and the presence of loose fragments, as well as concomitant injuries are crucial factors in choosing the adequate surgical approach.Long-term complications such as osteonecrosis of the femoral head, posttraumatic osteoarthritis and heterotopic ossification can lead to a relatively poor functional outcome. Cite this article: EFORT Open Rev 2021;6:1122-1131. DOI: 10.1302/2058-5241.6.210034.

Altered Secretome of Diabetic Monocytes Could Negatively Influence Fracture Healing-An In Vitro Study.

Diabetes mellitus is a main risk factor for delayed fracture healing and fracture non-unions. Successful fracture healing requires stimuli from different immune cells, known to be affected in diabetics. Especially, application of mononuclear cells has been proposed to promote wound and fracture healing. Thus, aim was to investigate the effect of pre-/diabetic conditions on mononuclear cell functions essential to promote osteoprogenitor cell function. We here show that pre-/diabetic conditions suppress the expression of chemokines, e.g., CCL2 and CCL8 in osteoprogenitor cells. The associated MCP-1 and MCP-2 were significantly reduced in serum of diabetics. Both MCPs chemoattract mononuclear THP-1 cells. Migration of these cells is suppressed under hyperglycemic conditions, proposing that less mononuclear cells invade the site of fracture in diabetics. Further, we show that the composition of cytokines secreted by mononuclear cells strongly differ between diabetics and controls. Similar is seen in THP-1 cells cultured under hyperinsulinemia or hyperglycemia. The altered secretome reduces the positive effect of the THP-1 cell conditioned medium on migration of osteoprogenitor cells. In summary, our data support that factors secreted by mononuclear cells may support fracture healing by promoting migration of osteoprogenitor cells but suggest that this effect might be reduced in diabetics.

Pantoprazole impairs fracture healing in aged mice.

Proton pump inhibitors (PPIs) belong to the most common medication in geriatric medicine. They are known to reduce osteoclast activity and to delay fracture healing in young adult mice. Because differentiation and proliferation in fracture healing as well as pharmacologic actions of drugs markedly differ in the elderly compared to the young, we herein studied the effect of the PPI pantoprazole on bone healing in aged mice using a murine fracture model. Bone healing was analyzed by biomechanical, histomorphometric, radiological and protein biochemical analyses. The biomechanical analysis revealed a significantly reduced bending stiffness in pantoprazole-treated animals when compared to controls. This was associated with a decreased amount of bone tissue within the callus, a reduced trabecular thickness and a higher amount of fibrous tissue. Furthermore, the number of osteoclasts in pantoprazole-treated animals was significantly increased at 2 weeks and decreased at 5 weeks after fracture, indicating an acceleration of bone turnover. Western blot analysis showed a lower expression of the bone morphogenetic protein-4 (BMP-4), whereas the expression of the pro-angiogenic parameters was higher when compared to controls. Thus, pantoprazole impairs fracture healing in aged mice by affecting angiogenic and osteogenic growth factor expression, osteoclast activity and bone formation.

Anterior approaches to the acetabulum: which one to choose?

Surgical treatment of acetabular fractures remains challenging even for experienced surgeons.Whilst the ilioinguinal and the Kocher-Langenbeck approach remain the standard procedures to expose the anterior or posterior aspects of the acetabulum, some modified anterior approaches for the stabilization of the acetabulum have been introduced.This article will provide an overview of approaches to the anterior aspect of the acetabulum and explain the efforts that have been made to improve the surgeon's options for certain fracture modifications, such as fractures with separation of the quadrilateral surface. Cite this article: EFORT Open Rev 2020;5:707-712. DOI: 10.1302/2058-5241.5.190061.