B7-1 and PlGF-1 are two possible new biomarkers to identify fracture-associated trauma patients at higher risk of developing complications: a cohort study.

BACKGROUND: Around 10% of fractures lead to complications. With increasing fracture incidences in recent years, this poses a serious burden on the healthcare system, with increasing costs for treatment. In the present study, we aimed to identify potential 'new' blood markers to predict the development of post-surgical complications in trauma patients following a fracture. METHODS: A total of 292 trauma patients with a complete three-month follow-up were included in this cohort study. Blood samples were obtained from 244 of these patients. Two complication groups were distinguished based on the Clavien-Dindo (CD) classification: CD grade I and CD grade III groups were compared to the controls (CD 0). The Mann-Whitney U test was used to compare the complication groups to the control group. RESULTS: Analysis of the patients' data revealed that risk factors are dependent on sex. Both, males and females who developed a CD III complication showed elevated blood levels of B7-1 (p = 0.015 and p = 0.018, respectively) and PlGF-1 (p = 0.009 and p = 0.031, respectively), with B7-1 demonstrating greater sensitivity (B7-1: 0.706 (male) and 0.692 (female), PlGF-1: 0.647 (male) and 0.615 (female)). Further analysis of the questionnaires and medical data revealed the importance of additional risk factors. For males (CD 0: 133; CD I: 12; CD III: 18 patients) alcohol consumption was significantly increased for CD I and CD III compared to control with p = 0.009 and p = 0.007, respectively. For females (CD 0: 107; CD I: 10; CD III: 12 patients) a significantly increased average BMI [kg/m2] from 25.5 to 29.7 with CD III was observed, as well as an elevation from one to three comorbidities (p = 0.003). CONCLUSIONS: These two potential new blood markers hold promise for predicting complication development in trauma patients. Nevertheless, further studies are necessary to evaluate the diagnostic utility of B7-1 and PlGF-1 in predicting complications in trauma patients and consider sex differences before their possible use as routine clinical screening tools.

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.

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.

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.

Anxiety and depression symptoms among gas and oil industry workers.

BACKGROUND: Oil and gas industry workers appear to suffer from anxiety and depression more frequently than the general population. AIMS: To establish the prevalence of depression and anxiety symptoms among offshore workers working for an oil and gas company and to identify the main stressors that lead to symptoms of these disorders. METHODS: One thousand seven hundred and forty-seven workers employed in an offshore oil and gas company in the Middle East completed the Generalized Anxiety Disorder (GAD-7) and Patient Health (PHQ-9) questionnaires. Anxiety and depressive symptoms were estimated from these surveys. RESULTS: Anxiety and depression symptoms were reported by nearly 15% of workers surveyed. Ordered logistic regression analyses showed that age, rotation length, years of service and local origin (versus expatriate) were significant predictors for symptoms of anxiety. With adjustment for age, older local workers had a lower risk of anxiety symptoms than expatriates. CONCLUSIONS: Younger workers, workers with longer rotations and those with fewer years of service were more likely to report anxiety symptoms. In addition, older local workers and expatriates had a lower prevalence of anxiety symptoms than younger local workers. Future recommendations should address improvements in psychological health of offshore workers in the gas and oil industries.

Predictors for secondary hip osteoarthritis after acetabular fractures-a pelvic registry study.

PURPOSE: Secondary hip osteoarthritis after acetabular fractures requiring total arthroplasty (THA) poses a huge burden on the affected patients as well as health systems. The present study aimed to assess risk factors associated with THA after acetabular fractures based on the data from the German Pelvic Trauma Registry. METHODS: Retrospective analysis of 678 acetabular fracture cases without concomitant pelvic ring fracture treated and followed-up between January 2004 and May 2015 at six large trauma centres. Multivariate Cox regression analysis was performed assessing the association of patient/treatment characteristics with THA likelihood at an average follow-up of 2.7 years (range 0.4-9.5 years; SD 1.8 years). RESULTS: Overall, the rate of secondary osteoarthritis was 19.8%. The likelihood for THA increased with 6% per age year (95% CI 1.04-1.09) and with 21% per millimetre subluxation (95%CI 1.09-1.33). This likelihood was 3.54 (95% CI 1.77-7.08) and 3.68 times (95% CI 1.87-7.47) higher if the posterior wall was involved and a contusion and/or impaction of the femoral head was present. Other covariates (sex, ISS, trauma type, AO/OTA and Letournel classification, initial displacement, surgical approach, intra-articular fragments, contusion and/or impaction to the acetabulum, reduction, intervention type, duration of surgery, soft tissue damage, residual fracture step/gap, and prevention of heterotopic ossifications) were not significantly associated (p > 0.15). CONCLUSIONS: Twenty percent of patients with acetabular fractures require THA. The associated risk factors are patient age, femoral head lesion/subluxation, and involvement of the posterior wall. The identified risk factors support previous research and should be minded when treatment of acetabular fractures is planned.

Surgical treatment of pelvic ring fractures in the elderly now and then: a pelvic registry study.

BACKGROUND: With the demographic change, the treatment of elderly patients has become a major issue for health systems worldwide. AIMS: The aim of this study was to analyze the change in the rate of surgical treatment of pelvic ring fractures in patients with an age of ≥60 years over a 22-year period depending on fracture type, age and sex. METHODS: Data of 5665 patients with an age of ≥60 years, who were treated for pelvic ring fractures from 1991 to 2013 in one of 31 hospitals participating in the German Pelvic Trauma Registry, were included. The registry is divided into four time periods: t 1 = 1991-1993, t 2 = 1997-2000, t 3 = 2001-2008 and t 4 = 2009-2013. Data had been collected prospectively and was analyzed retrospectively, stratified for age and sex of the patients as well as type of fracture and mode of therapy (surgical vs. conservative). RESULTS: There was a significant increase (p < 0.05) in the overall rate of surgical treatment. Nonetheless, during all time periods patients with an age of >70 years were significantly less frequently surgically treated compared to 60- to 70-year-olds. Regardless of the fracture type, the rate of surgical treatment was significantly higher (p < 0.05) in male compared to female patients during t 1. While this difference persisted for type A and type B fractures, the frequency of surgical treatment of type C fractures approximated in males and females. CONCLUSIONS: The present data indicate that the rate of surgical treatment of pelvic ring fractures in elderly patients has significantly increased over the 22-year period. Nonetheless, older patients (>70 years) as well as female patients are still less frequently surgically treated.

[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.

[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.

[Surgeon well-being and mindfulness-A narrative review on how come, for what reason, why in times of surgeon shortage]. / "Surgeon well-being" und "mindfulness" ­ ein narratives Review zum Wieso, Weshalb, Warum in Zeiten des Chirurg:innenmangels.

In the Anglo-American world the field of surgeon well-being is already very prominent, while in Germany it is still underrepresented. In this article, we aim to analyze the challenges and factors that affect the well-being of surgeons, including stress, burnout, workload, job satisfaction, autonomy, leadership, teamwork and work-life integration. Additionally, we discuss the connection between surgeon well-being and the shortage of new talent in surgery, which is currently being exacerbated by increasing treatment and physician demands, the age development of specialists and an overall high turnover. Finally, we propose several solutions that can be implemented at individual, institutional and systemic levels to promote and maintain the well-being of surgeons. These include improving working conditions, providing resources and support, promoting resilience and mindfulness and recognizing and appreciating achievements.

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.

"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.

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.

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.

[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.

[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.

[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.

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.

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.