Vitamin D3 deficiency and osteopenia in spastic paraplegia type 5 indicate impaired bone homeostasis.

Hereditary spastic paraplegia type 5 (SPG5) is an autosomal recessively inherited movement disorder characterized by progressive spastic gait disturbance and afferent ataxia. SPG5 is caused by bi-allelic loss of function mutations in CYP7B1 resulting in accumulation of the oxysterols 25-hydroxycholesterol and 27-hydroxycholesterol in serum and cerebrospinal fluid of SPG5 patients. An effect of 27- hydroxycholesterol via the estrogen and liver X receptors was previously shown on bone homeostasis. This study analyzed bone homeostasis and osteopenia in 14 SPG5 patients as a non-motor feature leading to a potential increased risk for bone fractures. T-Scores in CT bone density measurements were reduced, indicating osteopenia in SPG5 patients. Further, we analyzed various metabolites of bone homeostasis by ELISA in serum samples of these patients. We identified a lack of vitamin D3 metabolites (Calcidiol and Calcitriol), an increase in Sclerostin as a bone formation/mineralization inhibiting factor, and a decrease in cross-linked N-telopeptide of type I collagen (NTX), a marker indicating reduced bone resorption. As statin treatment has been found to lower oxysterol levels, we evaluated its effect in samples of the STOP-SPG5 trial and found atorvastatin to normalize the increased sclerostin levels. In summary, our study identified osteopenia as a non-motor feature in SPG5 and suggests the need for vitamin D3 substitution in SPG5 patients. Sclerostin may be considered a therapeutic target and biomarker in upcoming therapeutical trials in SPG5.

Salvage Algorithm for Deep Surgical Site Infections after HTO with Unstable Bone Situation Using a Hexapod System - Primary Results.

The incidence of deep surgical site infections following high tibial osteotomy (HTO) ranges between 0.4 to 4.7%. It is a severe complication with a high risk for poor clinical outcome. The aim of this study was to proof that a salvage algorithm for infected HTO with unstable bone situation leads to an infection-free status and bone union of the osteotomy and that correct limb alignment can be restored with good knee function.The study included seven patients with peri-implant infections following HTO. Infections occurred 83 ± 58.9 days (range: 24-191) after HTO. All patients underwent the "RESTORE" algorithm: patients received (1) REmoval of the HTO hardware and extensive debridement; (2) the osteotomy was STabilized with a hexapod external fixator (Taylor Spatial Frame, TSF); (3) the osteotomy gap was Opened; and (4) the alignment was REconstructed using the TSF, aiming for the intended limb alignment of the initial HTO. Patient-reported outcomes were assessed 22-36 months after removal of the TSF.After 24 weeks (range: 11-35), an infection-free status and bone healing were achieved. In all cases, the limb was saved, and the previously targeted mechanical axis of the lower limb was restored. All patients reached full extension of the knee joint and at least 110° of flexion. For KOOS: Symptoms 67.86 ± 18.1, Pain 73.41 ± 16.58, ADL 78.99 ± 21.32, Sports 52.14 ± 25.96, and QoL 41.96 ± 24.66. OKS 35.71 ± 8.8, SF-12 Physical Health 38.89 ± 10.3, and SF-12 Mental Health 46.86 ± 13.76.The "RESTORE" algorithm is a safe and effective salvage procedure. The concept allows for saving the limb and obtaining the previously planned limb alignment. Patient-reported outcome measures showed slightly lowered values than healthy samples, but substantially better values than patients awaiting HTO. Due to the possibility of initial full weight-bearing, the risk of higher morbidity caused by immobilization is minimized.

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.

AZU1: a new promising marker for infection in orthopedic and trauma patients?

Early and reliable detection of infection is vital for successful treatment. Serum markers such as C-reactive protein (CRP) and procalcitonin (PCT) are known to increase with a time lag. Azurocidin 1 (AZU1) has emerged as a promising marker for septic patients, but its diagnostic value in orthopedic and trauma patients remains unexplored. Between July 2020 and August 2023, all patients necessitating inpatient treatment for periprosthetic joint infection (PJI), peri-implant infection (II), soft tissue infection, chronic osteomyelitis, septic arthrodesis, bone non-union with and without infection were enrolled. Patients undergoing elective total joint arthroplasty (TJA) served as the control group. Blood samples were collected and analyzed for CRP, white blood cell count (WBC), PCT, and AZU1. Based on the inclusion and exclusion criteria 222 patients were included in the study (trauma = 38, soft tissue infection = 75, TJA = 33, PJI/II = 39, others = 37). While sensitivity and specificity were comparably high for AZU1 (0.734/0.833), CRP and PCT had higher specificity (0.542/1 and 0.431/1, respectively), and WBC a slightly higher sensitivity (0.814/0.455) for septic conditions. Taken together, the area under the curve (AUC) showed the highest accuracy for AZU1 (0.790), followed by CRP (0.776), WBC (0.641), and PCT (0.656). The Youden-Index was 0.57 for AZU1, 0.54 for CRP, 0.27 for WBC, and 0.43 for PCT. Elevated AZU1 levels effectively distinguished patients with a healthy condition from those suffering from infection. However, there is evidence suggesting that trauma may influence the release of AZU1. Additional research is needed to validate the diagnostic value of this new biomarker and further explore its potential clinical applications.

Classification and Incidence of Heterotopic Ossifications in Relation to NSAID Prophylaxis after Elbow Trauma.

Heterotopic ossification (HO) after elbow trauma can be responsible for significant motion restrictions. The study's primary aim was to develop a new X-ray-based classification for HO of the elbow. This retrospective study analyzed elbow injury radiographs from 138 patients aged 6-85 years (mean 45.9 ± 18) who underwent operative treatment. The new classification was applied at 6 weeks, 12 weeks, and 6 months postoperatively. The severity of HO was graded from 0 to 4 and localization was defined as r (radial), p (posterior), u (ulnar) or a (anterior) by two observers. The patients were categorized based on injury location and use of non-steroidal anti-inflammatory drugs (NSAIDs) for HO prophylaxis. The correlations between the generated data sets were analyzed using Chi-square tests (χ2) with a significance level of p < 0.05. The inter- and intraobserver reliability was assessed using Cohen's Kappa. In 50.7% of the evaluated X-rays, the formation of HO could be detected after 12 weeks, and in 60% after 6 months. The analysis showed a significant correlation between the injury's location and the HO's location after 12 weeks (p = 0.003). The use of an NSAID prophylaxis did not show a significant correlation with the severity of HO. The classification showed nearly perfect inter- (κ = 0.951, p < 0.001) and intrareliability (κ = 0.946, p < 0.001) according to the criteria of Landis and Koch. Based on the presented classification, the dimension and localization of HO in the X-ray image can be described in more detail compared to previously established classifications and, thus, can increase the comparability of results across studies.

[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.

Cilostazol Stimulates Angiogenesis and Accelerates Fracture Healing in Aged Male and Female Mice by Increasing the Expression of PI3K and RUNX2.

Fracture healing in the aged is associated with a reduced healing capacity, which often results in delayed healing or non-union formation. Many factors may contribute to this deterioration of bone regeneration, including a reduced 'angiogenic trauma response'. The phosphodiesterase-3 (PDE-3) inhibitor cilostazol has been shown to exert pro-angiogenic and pro-osteogenic effects in preclinical studies. Therefore, we herein analyzed in a stable closed femoral fracture model whether this compound also promotes fracture healing in aged mice. Forty-two aged CD-1 mice (age: 16-18 months) were daily treated with 30 mg/kg body weight cilostazol (n = 21) or vehicle (control, n = 21) by oral gavage. At 2 and 5 weeks after fracture, the femora were analyzed by X-ray, biomechanics, micro-computed tomography (µCT), histology, immunohistochemistry, and Western blotting. These analyses revealed a significantly increased bending stiffness at 2 weeks (2.2 ± 0.4 vs. 4.3 ± 0.7 N/mm) and an enhanced bone formation at 5 weeks (4.4 ± 0.7 vs. 9.1 ± 0.7 mm3) in cilostazol-treated mice when compared to controls. This was associated with a higher number of newly formed CD31-positive microvessels (3.3 ± 0.9 vs. 5.5 ± 0.7 microvessels/HPF) as well as an elevated expression of phosphoinositide-3-kinase (PI3K) (3.6 ± 0.8 vs. 17.4 ± 5.5-pixel intensity × 104) and runt-related transcription factor (RUNX)2 (6.4 ± 1.2 vs. 18.2 ± 2.7-pixel intensity × 104) within the callus tissue. These findings indicate that cilostazol accelerates fracture healing in aged mice by stimulating angiogenesis and the expression of PI3K and RUNX2. Hence, cilostazol may represent a promising compound to promote bone regeneration in geriatric patients.

Advances in Fracture Healing Research.

Despite a constant refinement of surgical techniques and bone fixation methods, up to 15% of fractures result in impaired healing or even develop a non-union [...].

Wearable activity data can predict functional recovery after musculoskeletal injury: Feasibility of a machine learning approach.

Delayed functional recovery after injury is associated with significant personal and socioeconomic burden. Identification of patients at risk for a prolonged recovery after a musculoskeletal injury is thus of high relevance. The aim of the current study was to show the feasibility of using a machine learning assisted model to predict functional recovery based on the pre- and immediate post injury patient activity as measured with wearable systems in trauma patients. Patients with a pre-existing wearable (smartphone and/or body-worn sensor), data availability of at least 7 days prior to their injury, and any musculoskeletal injury of the upper or lower extremity were included in this study. Patient age, sex, injured extremity, time off work and step count as activity data were recorded continuously both pre- and post-injury. Descriptive statistics were performed and a logistic regression machine learning model was used to predict the patient's functional recovery status after 6 weeks based on their pre- and post-injury activity characteristics. Overall 38 patients (7 upper extremity, 24 lower extremity, 5 pelvis, 2 combined) were included in this proof-of-concept study. The average follow-up with available wearable data was 85.4 days. Based on the activity data, a predictive model was constructed to determine the likelihood of having a recovery of at least 50 % of the pre-injury activity state by post injury week 6. Based on the individual activity by week 3 a predictive accuracy of over 80 % was achieved on an independent test set (F1=0,82; AUC=0,86; ACC=8,83). The employed model is feasible to assess the principal risk for a slower recovery based on readily available personal wearable activity data. The model has the potential to identify patients requiring additional aftercare attention early during the treatment course, thus optimizing return to the pre-injury status through focused interventions. Additional patient data is needed to adapt the model to more specifically focus on different fracture entities and patient groups.

Are there associations between hip geometry and bone quality? An analysis on 3074 adults from a general population.

INTRODUCTION: Patients with reduced bone mineral density and altered hip geometry are susceptible for hip pathologies. Knowledge on associations between bone properties and hip geometric parameters might facilitate identification of patients at risk for hip pathologies. The aim of the present study was to identify associations of bone properties assessed by quantitative ultrasound (QUS) at the heel and hip geometric parameters like center-edge angle (CE), neck-shaft angle (NSA) and alpha angle. MATERIALS AND METHODS: Hip geometric parameters (CE, NSA and alpha angle) of 3074 participants from the population-based Study of Health in Pomerania were assessed on magnetic resonance imaging. QUS was performed on both calcanei providing broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness-index. Based on the stiffness-index the individual osteoporotic fracture risk (low, moderate or high) was determined. Associations between QUS-based and hip geometric parameters were calculated in linear regression models adjusted for age, sex, body height and weight. Interactions of QUS markers with age and sex on hip geometric parameters were tested. RESULTS: Significant inverse associations between BUA (ß = - 0.068), SOS (ß = - 0.024) as well as stiffness-index (ß = - 0.056) and CE were present, while fracture risk was positively associated with CE (ß for high = 1.28 and moderate = 2.54 vs. low fracture risk). Interactions between BUA and sex as well as between SOS and age were detected in the models for CE. Furthermore, there was an inverse relation between fracture risk and NSA that was restricted to the moderate risk (ß for moderate vs. low fracture risk = - 0.60). There were no significant associations between QUS parameters and alpha angle. CONCLUSIONS: In the general population, several associations between QUS-based bone properties or fracture risk and hip geometry are present. Less dysplastic hips had a lower stiffness-index and a higher fracture risk, whereas more valgus hips had a lower fracture risk.

Advantages and Limitations of Diabetic Bone Healing in Mouse Models: A Narrative Review.

Diabetes represents a major risk factor for impaired fracture healing. Type 2 diabetes mellitus is a growing epidemic worldwide, hence an increase in diabetes-related complications in fracture healing can be expected. However, the underlying mechanisms are not yet completely understood. Different mouse models are used in preclinical trauma research for fracture healing under diabetic conditions. The present review elucidates and evaluates the characteristics of state-of-the-art murine diabetic fracture healing models. Three major categories of murine models were identified: Streptozotocin-induced diabetes models, diet-induced diabetes models, and transgenic diabetes models. They all have specific advantages and limitations and affect bone physiology and fracture healing differently. The studies differed widely in their diabetic and fracture healing models and the chosen models were evaluated and discussed, raising concerns in the comparability of the current literature. Researchers should be aware of the presented advantages and limitations when choosing a murine diabetes model. Given the rapid increase in type II diabetics worldwide, our review found that there are a lack of models that sufficiently mimic the development of type II diabetes in adult patients over the years. We suggest that a model with a high-fat diet that accounts for 60% of the daily calorie intake over a period of at least 12 weeks provides the most accurate representation.

Clinical Outcome of Carbon Fiber Reinforced Polyetheretherketone Plates in Patients with Proximal Humeral Fracture: One-Year Follow-Up.

BACKGROUND: Proximal humerus fractures are seen frequently, particularly in older patients. The development of new osteosynthesis materials is being driven by the high complication rates following surgical treatment of proximal humerus fractures. Plate osteosyntheses made of steel, titanium and, for several years now, carbon fiber-reinforced polyetheretherketone (CFR-PEEK) are used most frequently. METHODS: A prospective, randomized study was conducted in order to evaluate whether there are differences in the functional postoperative outcome when comparing CFR-PEEK and titanium implants for surgical treatment of proximal humerus fractures. The primary outcome of shoulder functionality 1 year after surgery was measured with the DASH score, the Oxford Shoulder Score, and the Simple Shoulder Test. RESULTS: Bony consolidation of the respective fracture was confirmed in all the patients included in the study within the scope of postoperative follow-up care. No significant differences in the DASH score, Oxford Shoulder Score, or Simple Shoulder Test were observed 1 year post-operatively when comparing the implant materials CFR-PEEK and titanium. CONCLUSIONS: There are no differences in terms of the functional outcome between CFR-PEEK plates and titanium implants 1 year after surgery. Studies on the long-term outcomes using CFR-PEEK plates in osteoporotic bone should be the subject of further research.

Parathyroid hormone stimulates bone regeneration in an atrophic non-union model in aged mice.

BACKGROUND: Non-union formation still represents a major burden in trauma and orthopedic surgery. Moreover, aged patients are at an increased risk for bone healing failure. Parathyroid hormone (PTH) has been shown to accelerate fracture healing in young adult animals. However, there is no information whether PTH also stimulates bone regeneration in atrophic non-unions in the aged. Therefore, the aim of the present study was to analyze the effect of PTH on bone regeneration in an atrophic non-union model in aged CD-1 mice. METHODS: After creation of a 1.8 mm segmental defect, mice femora were stabilized by pin-clip fixation. The animals were treated daily with either 200 mg/kg body weight PTH 1-34 (n = 17) or saline (control; n = 17) subcutaneously. Bone regeneration was analyzed by means of X-ray, biomechanics, micro-computed tomography (µCT) imaging as well as histological, immunohistochemical and Western blot analyses. RESULTS: In PTH-treated animals bone formation was markedly improved when compared to controls. This was associated with an increased bending stiffness as well as a higher number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD31-positive microvessels within the callus tissue. Furthermore, PTH-treated aged animals showed a decreased inflammatory response, characterized by a lower number of MPO-positive granulocytes and CD68-positive macrophages within the bone defects when compared to controls. Additional Western blot analyses demonstrated a significantly higher expression of cyclooxygenase (COX)-2 and phosphoinositide 3-kinase (PI3K) in PTH-treated mice. CONCLUSION: Taken together, these findings indicate that PTH is an effective pharmacological compound for the treatment of non-union formation in aged animals.

NET Formation Was Reduced via Exposure to Extremely Low-Frequency Pulsed Electromagnetic Fields.

Fracture-healing is a highly complex and timely orchestrated process. Non-healing fractures are still a major clinical problem and treatment remains difficult. A 16 Hz extremely low-frequency pulsed electromagnetic field (ELF-PEMF) was identified as non-invasive adjunct therapy supporting bone-healing by inducing reactive oxygen species (ROS) and Ca2+-influx. However, ROS and Ca2+-influx may stimulate neutrophils, the first cells arriving at the wounded site, to excessively form neutrophil extracellular traps (NETs), which negatively affects the healing process. Thus, this study aimed to evaluate the effect of this 16 Hz ELF-PEMF on NET formation. Neutrophils were isolated from healthy volunteers and exposed to different NET-stimuli and the 16 Hz ELF-PEMF. NETs were quantified using Sytox Green Assay and immunofluorescence, Ca2+-influx and ROS with fluorescence probes. In contrast to mesenchymal cells, ELF-PEMF exposure did not induce ROS and Ca2+-influx in neutrophils. ELF-PEMF exposure did not result in basal or enhanced PMA-induced NET formation but did reduce the amount of DNA released. Similarly, NET formation induced by LPS and H2O2 was reduced through exposure to ELF-PEMF. As ELF-PEMF exposure did not induce NET release or negatively affect neutrophils, the ELF-PEMF exposure can be started immediately after fracture treatment.

Translational evaluation of gait behavior in rodent models of arthritic disorders with the CatWalk device - a narrative review.

Arthritic disorders have become one of the main contributors to the global burden of disease. Today, they are one of the leading causes of chronic pain and disability worldwide. Current therapies are incapable of treating pain sufficiently and preventing disease progression. The lack of understanding basic mechanisms underlying the initiation, maintenance and progression of arthritic disorders and related symptoms represent the major obstacle in the search for adequate treatments. For a long time, histological evaluation of joint pathology was the predominant outcome parameter in preclinical arthritis models. Nevertheless, quantification of pain and functional limitations analogs to arthritis related symptoms in humans is essential to enable bench to bedside translation and to evaluate the effectiveness of new treatment strategies. As the experience of pain and functional deficits are often associated with altered gait behavior, in the last decades, automated gait analysis has become a well-established tool for the quantitative evaluation of the sequalae of arthritic disorders in animal models. The purpose of this review is to provide a detailed overview on the current literature on the use of the CatWalk gait analysis system in rodent models of arthritic disorders, e.g., Osteoarthritis, Monoarthritis and Rheumatoid Arthritis. Special focus is put on the assessment and monitoring of pain-related behavior during the course of the disease. The capability of evaluating the effect of distinct treatment strategies and the future potential for the application of the CatWalk in rodent models of arthritic disorders is also addressed in this review. Finally, we discuss important consideration and provide recommendations on the use of the CatWalk in preclinical models of arthritic diseases.

Cilostazol promotes blood vessel formation and bone regeneration in a murine non-union model.

Non-unions represent a major complication in trauma and orthopedic surgery. Many factors contribute to bone regeneration, out of which an adequate vascularization has been recognized as crucial. The phosphodiesterase-3 (PDE-3) inhibitor cilostazol has been shown to exert pro-angiogenic and pro-osteogenic effects in a variety of preclinical studies. Hence, we herein investigated the effects of cilostazol on bone regeneration in an atrophic non-union model in mice. For this purpose, a 1.8 mm femoral segmental defect was stabilized by pin-clip fixation and the animals were treated daily with 30 mg/kg body weight cilostazol or saline (control) per os. At 2, 5 and 10 weeks after surgery the healing of femora was analyzed by X-ray, biomechanics, photoacoustic imaging, and micro-computed tomography (µCT). To investigate the cellular composition and the growth factor expression of the callus tissue additional histological, immunohistochemical and Western blot analyses were performed. Cilostazol-treated animals showed increased bone formation within the callus, resulting in an enhanced bending stiffness when compared to controls. This was associated with a more pronounced expression of vascular endothelial growth factor (VEGF), a higher number of CD31-positive microvessels and an increased oxygen saturation within the callus tissue. Furthermore, cilostazol induced higher numbers of tartrate-resistant acidic phosphate (TRAP)-positive osteoclasts and CD68-positive macrophages. Taken together, these findings demonstrate that cilostazol is a promising drug candidate for the adjuvant treatment of atrophic non-unions in clinical practice.

"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.

MRI-based torsion measurement of the lower limb is a reliable and valid alternative for CT measurement: a prospective study.

PURPOSE: The aim of this study was to compare MRI-based torsion measurements of the lower limb to a well-established CT-based assessment in a prospective inter- and intraindividual approach. METHODS: A total of 26 patients (age 28.8 years ± 11.0) were enrolled beginning in January 2021 until August 2022. Inclusion criteria were the clinical indication for torsion measurement of the lower limb. CT and MRI imaging were performed with a standard operating procedure, to ensure that all patients were examined in a standardized position. The examinations were planned on a coronal scout view based on prominent anatomical landmarks. Femoral and tibial torsion were measured individually. Torsion measurements were analysed twice: immediately after examination and after 3 weeks. Subsequently, intra-rater and parallel test reliability was calculated accordingly. RESULTS: High significant results for CT and MRI measurements for both tibia (MRI: r = 0.961; p ≤ 0.001; CT: r = 0.963; p ≤ 0.001) and femur (MRI: r = 0.980; p ≤ 0.001; CT: r = 0.979; p ≤ 0.001) were obtained by calculated intra-rater reliability, showing that measurements were highly consistent for MRI and CT, respectively. Parallel test reliability for time point 1 as well as time point 2 was also highly significant and ranged from r = 0.947 to r = 0.972 (all with p ≤ 0.001, respectively) for both tibia and femur, showing a high concordance between the two measurements. CONCLUSION: Measurement of tibial as well as femoral torsion was comparable for CT and MRI measurement. Therefore, this study supports MRI measurement as an equivalent alternative for CT measurement concerning torsional malalignment to reduce exposure to radiation. LEVEL OF EVIDENCE: Level II.