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Background: While postoperative malrotation in the subtrochanteric region is a well-known problem, malrotation after osteosynthesis in proximal femoral fractures has not been extensively studied. In this context, many methods for perioperatively assessment of femoral torsion have been described, but none of them is applicable in the basicervical region of the proximal femur. As an important difference in femoral neck fractures, the discontinuous neck fails to serve as a significant "pointer" for measurements and malfunctions to be placed in relation to the condylar plane. Considering postoperative maltorsion at any location as a substantial negative effect on patients' outcome and functional expectations, precise and patient-friendly rotation measurement standards in femoral neck fractures are desired in clinical practice. Recently, a novel computed tomography (CT) based geometric technique was described named "direct measurement" with promising results covering this diagnostic disparity, but still requires validation. Thus, we aimed to validate the previously described technique using a controlled range of displacement in a femoral neck fracture Sawbone® model., Methods and Findings: A goniometer was designed to set retro- and anteversion of the proximal femur in a reproducible manner. Prospectively, all femurs underwent a CT scan and were measured 3D for displacement. The interclass correlation between the CT measurements and the goniometer measurements was calculated and was found to be very high (1.00, 95% confidence interval: 0.99-1.00; p < 0.001). For the mean of all measurements, the Pearson's correlation was 1.00 (p < 0.001). No significant differences in the measurements of both investigators were observed, with 20° of retroversion not significant (-1.20 ± 1.71; 95% confidence interval: -2.43-0.03; p = 0.054)., Conclusion: This CT-based 3D measurement technique may allow for perioperative malrotation assessment in basicervical femoral neck fractures and appears to be feasible in femoral neck fractures when it comes to rare cases of osteosynthesis. Further investigations are still needed to define the thresholds of malrotation provoking functional impairment after osteosynthesis in basicervical femoral neck fractures., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Liodakis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Extensive diaphyseal and metaphyseal bone defects continue to pose a major challenge for orthopedic trauma surgeons. Various treatment options have been described for the biological reconstruction of these defects. The most frequently used methods are bone segment transport, the Masquelet technique and 3D printed scaffolds. As far as the Masquelet technique is concerned, in the first stage spacers, such as polymethyl methacrylate (PMMA), calcium sulfate or polypropylene are inserted into the bone defects to induce a foreign body membrane. In the second stage the bone defect surrounded by the induced membrane is filled with autologous cancellous bone. The time interval between the first and second interventions is usually 4-8 weeks whereby the induced membranes do not lose their bioactivity even with a latency period longer than 8 weeks. Three-dimensional printed scaffolds are increasingly used but large clinical studies are lacking in order to show the exact role of this procedure in the reconstruction of bone defects., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Interdisciplinary case conferences are well-established in the field of oncology in order to provide the best possible treatment for patients with complex disease patterns which overlap several disciplines., Methods: After studying the available literature the aims, indications, frequency, patient enrolment and documentation modalities, disciplines necessary to create the reconstruction plan and evaluation parameters of the board, were agreed in an interdisciplinary discussion among colleagues. The utilization of the extremity board and demographic features of the cases presented in the extremity board within the first 6 months were subsequently descriptively analyzed., Results: The agreed primary aim of an extremity board is the timely and transparent preparation of a high-quality holistic reconstruction plan for optimized treatment of a challenging patient collective with complex injuries of the extremities. Decisive interfaces of an extremity board are the participation of interdisciplinary disciplines, established enrolment and documentation modalities and a longitudinal analysis of parameters of the acute medical treatment, the long-term function and quality of life of those affected. The patient collective so far mostly includes men under 40 years old with traumatic soft tissue defects and combined injuries. On average, reconstruction plans for 1-2 patients were approved in an interdisciplinary team per session., Conclusion: The extremity board serves as a platform for coordinated planning of treatment for patients with complex injuries. The limited personnel and time resources represent the greatest challenge for the successful implementation. The extremity board enables a high degree of interdisciplinary networking. The digital registration and documentation modality within the internal hospital documentation system is of utmost relevance. The preparation of the reconstruction plan is of decisive importance for the qualitative success of treatment and the restoration of function. The longitudinal analysis of appropriate parameters is imperative to measure the quality of treatment., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: High clinical success rates have been reported with the Masquelet technique in the treatment of traumatic bone loss. An increasing number of studies suggest that various factors can influence the properties of induced membranes. Goal of this systematic review is to answer the following questions: (1) which are the ideal spacer properties (material, surface topography, antibiotic supplementation) to booster the quality and osteogenic potential of induced membranes? (2) what is the ideal time to perform the second-stage operation?, Methods: A systematic search using the keywords "((Masquelet) OR (Induced Periosteum)) AND ((Spacer) OR (Time))" was performed in PubMed, Embase and Cochrane Library according to PRISMA guidelines. Studies published up to the 23rd of February 2022 were included and assessed independently by two reviewers., Results: Thirteen animal and 1 clinical studies were identified to address the above questions. Spacer materials used were PMMA, silicone, titanium, polypropylene, PVA, PCL and calcium sulfate. With the exception of PVA sponges, all solid materials could induce membranes. Low union rates have been reported with titanium and rough surfaced spacers. Scraping of the inner surface of the IM also increased bony union rates. In terms of the ideal timing to perform the second-stage evidence suggests that membranes older than 8 weeks continue to have regenerative capacities similar to younger ones., Conclusion: Membranes induced by smooth PMMA spacers loaded with low concentrations of antibiotics showed powerful osteogenic properties. Other materials such as Polypropylene or Calcium sulfate can also be used with good results. Despite current recommendation to perform the second stage operation in 4-8 weeks, membranes older than 8 weeks seem to have similar regenerative capacities to younger ones., (© 2022. The Author(s).)

Purpose: Enobosarm (EN), a selective androgen receptor modulator and raloxifene (RAL), a selective estrogen receptor modulator, have been shown to improve bone tissue in osteoporotic males. The present study evaluated the effects of a combination therapy of EN and RAL on bone properties in orchiectomized rats compared to the respective single treatments., Methods: Eight-month-old male Sprague-Dawley rats were either left intact (Non-Orx) or orchiectomized (Orx). The Orx rats were divided into four groups (n = 15 each): 1) Orx, 2) EN treatment (Orx + EN), 3) RAL treatment (Orx + RAL), 4) combined treatment (Orx + EN + RAL). EN and RAL (0.4 mg and 7 mg/kg body weight/day) were applied immediately after Orx with a soy-free pelleted diet for up to 18 weeks. The lumbar spine and femora were examined by micro-CT, biomechanical, histomorphological, ashing, and gene expression analyses., Results: EN exhibited an anabolic effect on bone, improving some of its parameters in Orx rats, but did not affect biomechanical properties. RAL exhibited antiresorptive activity, maintaining the biomechanical and trabecular parameters of Orx rats at the levels of Non-Orx rats. EN + RAL exerted a stronger effect than the single treatments, improving most of the bone parameters. Liver weight increased after all treatments; the kidney, prostate, and levator ani muscle weights increased after EN and EN + RAL treatments. BW was reduced due to a decreased food intake in the Orx + RAL group and due a reduced visceral fat weight in the Orx + EN + RAL group., Conclusion: The EN + RAL treatment appeared to be promising in preventing male osteoporosis, but given the observed side effects on liver, kidney, and prostate weights, it requires further investigation., (© 2022. The Author(s).)

Background: Navigation systems are supposed to increase precision and support surgeons while they perform certain interventions. 2D, or nowadays 3D, systems are used in image-based approaches. Image-free navigation uses 3D printing., Indications: There are several studies on navigation procedures in trauma surgery. In contrast to limb surgery, the use of 3D navigation in pelvic and spine surgery is already well established. Navigation is especially regularly used to treat fractures of the posterior pelvic ring and for posterior stabilization of the cervical spine., Requirements: To be able to utilize navigation systems optimally, the learning curve should be completed, and the technique should be used regularly. In addition, the surgeon should know the surgical technique without navigation in order to recognize potential errors of the navigation., Advantages and Disadvantages: Advantages include increased patient safety, reduction in radiation exposure and less invasive surgical procedures. However, among other disadvantages, initial costs are high., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: Selective androgen and estrogen receptor modulators, ostarine (OST) and raloxifen (RAL), reportedly improve muscle tissue and offer therapeutic approaches to muscle maintenance in the elderly. The present study evaluated the effects of OST and RAL and their combination on musculoskeletal tissue in orchiectomized rats., Methods: Eight-month-old Sprague Dawley rats were analyzed. Experiment I: (1) Untreated non-orchiectomized rats (Non-ORX), (2) untreated orchiectomized rats (ORX), (3) ORX rats treated with OST during weeks 0-18 (OST-P), (4) ORX rats treated with OST during weeks 12-18 (OST-T). Experiment II: 1) Non-ORX, (2) ORX, 3) OST-P, (4) ORX rats treated with RAL, during weeks 0-18 (RAL-P), 5) ORX rats treated with OST + RAL, weeks 0-18 (OST + RAL-P). The average daily doses of OST and RAL were 0.4 and 7 mg/kg body weight (BW). Weight, fiber size, and capillarization of muscles, gene expression, serum markers and the lumbar vertebral body were analyzed., Results: OST-P exerted favorable effects on muscle weight, expression of myostatin and insulin growth factor-1, but increased prostate weight. OST-T partially improved muscle parameters, showing less effect on the prostate. RAL-P did not show anabolic effects on muscles but improved body constitution by reducing abdominal area, food intake, and BW. OST + RAL-P had an anabolic impact on muscle, reduced androgenic effect on the prostate, and normalized food intake. OST and RAL improved osteoporotic bone., Conclusions: The OST + RAL treatment appeared to be a promising option in the treatment of androgen-deficient conditions and showed fewer side effects than the respective single treatments., (© 2022. The Author(s).)

The technique of 3D printing offers a high potential for further optimization of spinal surgery. This new technology has been published for different areas in the field of spinal surgery, e.g. in preoperative planning, intraoperative use as well as to create patient-specific implants. For example, it has been demonstrated that preoperative 3‑dimensional visualization of spinal deformities is helpful in planning procedures. Moreover, insertion of pedicle screws seems to be more accurate when using individualized templates to guide the drill compared to freehand techniques. This review summarizes the current literature dealing with 3D printing in spinal surgery with special consideration of the current applications, the limitations and the future potential., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background:  Cage implantations and autologous pelvic bone grafts are common surgical procedures to fuse the spine in cases of spinal disorders such as traumatic fractures or degenerative diseases. These surgical methods are designed to stably readjust the spine and to prevent late detrimental effects such as pain or increasing kyphosis. Benefits of these surgical interventions have been evaluated, but the long-term well-being of patients after the respective treatments has not yet been examined. This study was designed to evaluate the clinical outcome for patients who received iliac crest or cage implantations., Material and Methods:  Forty-six patients with traumatic fractures after they obtained an anterior fusion in the thoracic or lumbar spine (12 cages; mean age: 54.08 years; 34 pelvic bone grafts; mean age: 42.18 years) were asked to participate in the survey using a precast questionnaire according the Visual Analog Scale (VAS) Spine Score. Twenty-nine of them provided the data requested., Results:  Evaluation of the VAS scores of the patients, reporting at least 1 year after the surgery, revealed that cage implantations led to significantly better results with respect to all aspects of their daily life such as pain sensing, capability to undertake physical activities and exercise as compared with patients with autologous pelvic bone graft. Patients with autologous pelvic bone graft treatment reported a particularly poor overall satisfaction level concerning their long-term well-being., Conclusions:  Patients with cage implantation reported a higher degree of long-term well-being. The data provide evidence for a positive impact on the postsurgery quality of life after cage implantation., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: The treatment of pediatric femoral shaft fractures has undergone an increasing change in recent years. The previously predominant treatment procedures were extensively replaced by minimally invasive techniques (e.g. elastic stable intramedullary nailing, ESIN). The aim of this study was the comparison of complication rates depending on patient factors as well as various treatment procedures., Material and Methods: This study involved a retrospective X‑ray morphometric evaluation of data. The patient files and X‑rays of 101 children who were treated at 2 level I trauma centers were analyzed., Results: Conservative treatment was carried out in 19% of the cases. Among the surgical procedures the ESIN technique was predominant (n = 60). Complications that needed revision occurred in 10% of the children after conservative treatment. Revision surgery had to be carried out in more than 6% of the cases in children who were surgically treated. Among the surgical procedures ESIN stabilization demonstrated the lowest revision rate with only 3%. Children under three years and adolescents had a higher risk for developing complications. If the ESIN wires used were too thin in relation to the diameter of the medullary cavity there was an increased probability of complications of around 30%., Conclusion: This study revealed a moderate risk of complications in the treatment of femoral shaft fractures in children. The risk of complications after external fixation and conservative treatment was the highest in this study. Overall, the ESIN technique showed the lowest risk of complications. The results of this study could confirm the known limitations of the ESIN technique depending on age and body weight., (© 2021. The Author(s).)

Spondylodiscitis and postoperative wound infections are the most frequent infectious diseases of the thoracic and lumbar spine. Every spinal surgeon will come into contact with such patients during his or her career. Knowledge particularly of the diagnostics, conservative and surgical treatment as well as microbiological considerations of antibiotic treatment are therefore of particular importance and are explained in this article., (© 2021. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objectives: Early diagnosis of infections is pivotal in critically ill patients. Innovative gene expression-based approaches promise to deliver precise, fast, and clinically practicable diagnostic tools to bedside. This study aimed to validate the SepsisMetaScore, an 11-gene signature previously reported by our study group, in a representative longitudinal cohort of trauma patients., Design: Prospective observational cohort study., Setting: Surgical ICUs of the University Medical Center Goettingen, Germany., Patients: Critically ill patients with severe traumatic injuries., Interventions: None., Measurements and Main Results: Paired box gene (PAXgene) RNA blood tubes were drawn at predefined time points over the course of disease. The performance of the SepsisMetaScore was tested using targeted polymerase chain reaction and compared with Procalcitonin using area under the receiver operating characteristics analyses. The SepsisMetaScore showed significant differences between infected and noninfected patients (n = 52). It was able to accurately discriminate infectious from noninfectious acute inflammation with an area under the receiver operating characteristics of 0.92 (95% CI, 0.85-0.99) and significantly outperformed Procalcitonin (area under the receiver operating characteristics curve = 0.53; 95% CI, 0.42-0.64) early in the course of infection (p = 0.014)., Conclusions: We demonstrated the clinical utility for diagnosis of infections with higher accuracy using the SepsisMetaScore compared with Procalcitonin in a prospective cohort of severe trauma patients. Future studies should assess whether the SepsisMetaScore may substantially improve clinical practice by accurate differentiation of infections from sterile inflammation and identification of patients at risk for sepsis. Our results support further investigation of the SepsisMetaScore for the development of tailored precision treatment of critically ill patients., Competing Interests: Drs. Thair and Sweeney are employees of, and shareholders in, Inflammatix, Inc. Drs. Thair, Sweeney, and Khatri received funding from Inflammatix, Inc, Burlingame, CA. Inflammatix is developing the SepsisMetaScore as part of a broader test for commercial use (HostDx-Sepsis; Inflammatix). Dr. Quintel also received funding from Xenies/Fresenius, B.Braun, and Baxter. Dr. Khatri is a shareholder in and a consultant to Inflammatix; he is funded, in part, by the Bill and Melinda Gates Foundation (OPP1113682); the National Institute of Allergy and Infectious Diseases grants 1U19AI109662, U19AI057229, and 5R01AI125197; Department of Defense contracts W81XWH-18-1-0253 and W81XWH1910235; and the Ralph & Marian Falk Medical Research Trust. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background and Objectives: Stabilization of the spine by cage implantation or autologous pelvic bone graft are surgical methods for the treatment of traumatic spine fractures. These methods serve to stably re-adjust the spine and to prevent late detrimental effects such as pain or increasing kyphosis. They both involve ventral interventions using interbody fusion to replace the intervertebral disc space between the vertebral bodies either by cages or autologous pelvic bone grafts. We examined which of these methods serves the patients better in terms of bone fusion and the long-term clinical outcome. Materials and Methods: Forty-six patients with traumatic fractures (12 cages; mean age: 54.08/34 pelvic bone grafts; mean age: 42.18) who received an anterior fusion in the thoracic or lumbar spine were included in the study. Postoperative X-ray images were evaluated, and fusion of the stabilized segment was inspected by two experienced spine surgeons. The time to discharge from hospital and gender differences were evaluated. Results: There was a significant difference of the bone fusion rate of patients with autologous pelvic bone grafts in favor of cage implantation ( p = 0.0216). Also, the stationary phase of patients who received cage implantations was clearly shorter (17.50 days vs. 23.85 days; p = 0.0089). In addition, we observed a significant gender difference with respect to the bony fusion rate in favor of females treated with cage implantations ( p < 0.0001). Conclusions: Cage implantations after spinal fractures result in better bony fusion rates as compared to autologous pelvic bone grafts and a shorter stay of the patients in the hospital. Thus, we conclude that cage implantations rather than autologous pelvic bone grafts should be the preferred surgical treatment for stabilizing the spine after fracture.

Background: In previous studies, we reported the beneficial impact of two lipoxygenase-inhibitors, Baicalein and Zileuton, on osteoporotic bone in a postmenopausal rat model. Whereas subcutaneous Baicalein predominantly improved cortical bone, Zileuton enhanced vertebral and femoral trabecular bone. In this study, we aimed to reveal whether the oral administration of Baicalein caused similar effects on bone and whether a combined administration of Baicalein and Zileuton could act synergistically to ameliorate the formerly reported effects in the musculoskeletal system., Methods: We treated ovariectomized (OVX) female Sprague-Dawley rats either with Baicalein (10mg/kg BW), Zileuton (10mg/kg BW) or a combination of both (each 10mg/kg BW) for 13 weeks and compared with untreated OVX and NON-OVX groups (n=12-16 rats per group). Lumbar vertebral bodies and femora were analyzed. Tibiae were osteotomized, plate-stabilized (at week 8 after OVX) and likewise analyzed by biomechanical, histological, micro-computed tomographical and ashing tests. The skeletal muscle structure was analyzed., Results: Oral administration of Baicalein did not confirm the reported favorable cortical effects in neither vertebra nor femur. Zileuton showed a beneficial effect on trabecular vertebra, while the femur was negatively affected. Callus formation was enhanced by all treatments; however, its density and biomechanical properties were unaltered. Lipoxygenase inhibition did not show a beneficial effect on skeletal muscle. The combination therapy did not ameliorate OVX-induced osteoporosis but induced even more bone loss., Conclusions: The preventive anti-osteoporotic treatments with two lipoxygenase inhibitors applied either alone or in combination showed no benefit for the musculoskeletal system in estrogen deficient rats., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Saul, Hohl, Franz, Meyer, Taudien, Roch, Sehmisch and Komrakova.)

Hexaploid wheat (Triticum aestivum L.) is a natural allopolyploid and provides a usable model system to better understand the genetic mechanisms that underlie allopolyploid speciation through the hybrid genome doubling. Here we aimed to identify the contribution of chromosome 1D in the development and evolution of hexaploid wheat. We identified and mapped a novel DEFECTIVE ENDOSPERM-D1 (Dee-D1) locus on 1DL that is involved in the genetic control of endosperm development. The absence of Dee-D1 leads to non-viable grains in distant crosses and alters grain shape, which negatively affects grain number and thousand-grain weight. Dee-D1 can be classified as speciation locus with a positive effect on the function of genes which are involved in endosperm development in hybrid genomes. The presence of Dee-D1 is necessary for the normal development of endosperm, and thus play an important role in the evolution and improvement of grain yield in hexaploid wheat.

Enobosarm (ostarine, MK-2866, or GTx-024) is a non-steroidal selective androgen receptor modulator. This study evaluated the effect of various regimens of enobosarm (EN) on bone healing in an orchiectomized rat model for aged male osteoporosis and compared it to testosterone (T) treatment. Ninety eight-month-old male Sprague Dawley rats were either orchiectomized (Orx) or left intact (Non-Orx) and divided into groups (n = 15/group): (1) Non-Orx; (2) Orx; (3) Orx+T-th; (4) Orx+EN-th; (5) Orx+T-pr; and (6) Orx+EN-pr. Prophylaxis (Pr) treatments were applied immediately after Orx for up to 18 weeks. Therapy (Th) treatments were applied 12 weeks after Orx for up to 6 weeks. Bilateral tibia osteotomy with plate osteosynthesis was performed 12 weeks after Orx in all groups. EN and T were mixed with the diet; the daily dosage was 0.35 ± 0.06 and 41 ± 8 mg/kg BW, respectively. Both T treatments improved bone healing by increasing callus volume and area, bone volume and density, and cortical width; they had no effect on prostate or levator ani weight. EN-pr increased the callus area and callus density and decreased cortical density, but increased prostate weight. The effect of T-pr and T-th on bone was stronger than EN-pr. EN-th affected bone healing negatively by reducing callus density and area and delaying osteotomy bridging. Levator ani weight was increased in both EN groups. EN treatment after fracture is not advisable in aged males. EN-pr treatment as a therapy for bone healing in men could be further investigated; endocrinological side effects must be closely monitored.

In postmenopausal women, hormonal decline changes muscle function and structure. The non-steroidal selective androgen receptor modulators (SARMs) Ostarine (OS) and Ligandrol (LG) have been shown to increase muscle mass and physical function while showing a relative low risk profile. Information about their effects on muscle structure and metabolism is lacking. To analyze this, two experiments were performed using ovariectomized rats as a standard model for postmenopausal conditions. In each experiment, 3-month old Sprague-Dawley rats were divided into five groups ( n = 12 to 15). One group remained intact (Non-OVX), the other four groups were ovariectomized (OVX) and remained untreated for eight (OS Experiment) or nine (LG Experiment) weeks. Thereafter, rats of three of the four OVX groups were treated with OS or LG (with doses of 0.04, 0.4, or 4 mg/kg body weight/day) for 5 weeks. Then, uterus, gastrocnemius, and soleus muscles were weighed, fiber size, capillary density, and enzyme activity (lactate dehydrogenase [LDH], citrate synthase [CS], and complex I) were analyzed. In the LG experiment, intramuscular fat content was determined in the quadriceps femoris muscle. All OS treatments resulted in a higher capillary density in the gastrocnemius and longissimus muscles compared with the Non-OVX and the OVX rats, whereas all LG treatments showed a higher capillary density compared with the Non-OVX group. Muscle fiber size and distribution patterns were not changed under either SARM. The CS activity was higher in the longissimus muscle under OS treatment. LG resulted in a higher activity of CS in the gastrocnemius and of LDH in the longissimus muscle. Both SARMs showed an uterotrophic effect, OS at 4 and 0,4 mg dosages, LG at 4 mg dosage. In sum, beneficial effect on muscle vascularization was observed for both SARMs with a stronger impact for OS. LG showed more effect on muscle metabolism. However, a higher muscle weight and intramuscular fat content observed after LG treatment (4 mg) as well as an uterotrophic effect of both SARMs at higher dosages could be considered as an unfavorable side effects and might be a limitation for their application at these dosages., (Copyright © 2020 Roch, Henkies, Carstens, Krischek, Lehmann, Komrakova and Sehmisch.)

Background: The number of elderly patients among the severely injured has been increasing continuously. It has been suggested that an increased life expectancy and a higher level of activity and mobility in older ages could explain this observation. Elderly trauma patients have relevant higher mortality rates and poorer functional outcomes. The reasons remain unclear. The aim of this study was to look for differences in the management of severely injured elderly patients compared to younger age groups and to evaluate their potential impact on outcome., Methods: The TraumaRegister DGU ® is a multicenter database that documents de-identified data of severely injured patients since 1993. Trauma cases documented between 2009 and 2016 with an ISS ≥ 9 were divided in four age groups. The groups were compared with respect to mechanism of injury, pattern of injury, severity of injury, management and outcome., Results: The analysis of 126,015 severely injured patients showed that 37.5% of the population were elderly patients (≥ 60 years). Their rate actually increased every year by 1.7%. The elderly trauma patients experience different mechanisms of injury (more low energy trauma) and different pattern of injuries (more brain trauma, less abdominal and extremity injuries). Evaluating the management of patients showed that elderly patients have lower intubation rates and less volume replacement in the prehospital setting. Diagnostic interventions like CT scans in the emergency room were performed more restrictively. Elderly trauma patients also received fewer surgical interventions for brain injuries, pelvic fractures and femur fractures. Their hospital mortality rates were higher., Conclusions: Severely injured elderly patients are treated with a more "wait and see approach" resulting in higher mortality rates. We suggest that this population needs a more "aggressive management" to improve their outcome, if the wish to perform complete treatment including surgical procedures and intensive care medicine has not been excluded by the patients or their legal guardian.

Non-steroidal selective androgen receptor modulators, including ostarine, have been developed as an alternative to steroidal hormones. Ostarine has shown a beneficial effect on bone in experimental studies, but no data regarding the effect of ostarine on bone healing have yet been reported. We investigated effects of ostarine on bone healing in ovariectomized rats. Sprague-Dawley rats (3 months old) were ovariectomized (Ovx, n = 46) or left intact (Non-Ovx, n = 10). After 8 weeks, an osteotomy of the tibia metaphysis was created in all rats, and the Ovx rats were divided into four groups: untreated Ovx (n = 10) and three Ovx groups (each of 12 rats) treated with ostarine at doses of 0.04, 0.4, or 4 mg/kg BW (OS-0.04, OS-0.4, and OS-4 groups). Five weeks later, bone healing was analyzed. The OS-4 dose enhanced callus formation, increased callus density, accelerated bridging time of the osteotomy, and elevated alkaline phosphatase gene expression in callus and its protein expression in serum. In the Ovx group, most of the callus parameters were diminished. All OS treatments increased the weight of the gastrocnemius muscle, but only partly enhanced uterus weight in OS-0.4 and OS-4. Serum cholesterol level was reduced, and serum phosphorus was elevated in OS-0.04 and OS-4. Ostarine appeared to have a positive effect on early bone healing in ovariectomized rats. Considering its favorable effect on non-osteotomized bone and muscle, this treatment could be further explored as a therapy for osteoporosis. However, possible metabolic side effects should first be evaluated.

Background:  The cestode Echinococcus granulosus causes hydatid disease. In addition to manifestations in the liver and lung, it can lead to cystic lesions in the spine., Case Description:  We report a 42-year-old male patient with primary hydatid disease in the eighth thoracic vertebra. The only clinical symptom was chronic back pain. Although laboratory findings were normal, imaging displayed lytic destruction that raised the suspicion of a metastatic disease. Diagnostics of the thoraces and abdomen did not reveal other pathologic abnormalities. Follow-up magnetic resonance imaging (MRI) depicted a progressive compression of the spinal cord and inhomogeneous structure in the fat-suppressed sequences. Because the Jamshidi biopsy was inconclusive, the tumor board recommended surgery. Dorsal decompression, spondylodesis of T6-T10, and vertebral column resection of T8 with complete cyst removal were performed. The resected vertebrae showed a mucous-like lesion with white granular tissue interfusing the whole vertebral body. A pathologic examination and enzyme-linked immunosorbent assay confirmed E. granulosus . Thus chemotherapy with albendazole was initiated. A follow-up MRI of the whole spine confirmed complete remission and found no additional resettlements. The patient's back pain was resolved without neurologic deficits., Conclusions:  For lytic manifestations of the vertebral column, hydatid cysts should be considered a differential diagnosis in addition to malignant metastasis, tuberculosis, and osteomyelitis. Thorough surgical resection and strict follow-up are necessary., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: We evaluated the prevalence and influence of chronic hyponatremia in patients with low energy trauma. We also investigated the influence of medication and diseases on hyponatremia., Material and Methods: This retrospective study included 314 cases of proximal femoral fracture due to low energy trauma. Patients were treated in the University Medical Center Goettingen within 3 years. Hyponatremia was defined as serum sodium <135 mmol/L at admission., Results: Overall, 15.6% of patients in the low energy trauma group had hyponatremia. Among patients older than 80 years, women showed distinctly higher rates of hyponatremia (female: 16.4%; male: 5.9%). In contrast only 4.7% of patients who underwent elective hip arthroplasty showed hyponatremia. Patients on sartanes and aldosterone antagonists showed significantly higher rates of hyponatremia. Alcoholism was significantly associated with hyponatremia., Conclusions: We confirmed a high prevalence of chronic hyponatremia in patients with fractures due to low energy trauma. Our data underscore chronic hyponatremia as a contributing factor to hip fractures. Women older than 80 have a higher risk of developing hyponatremia. Sartanes, aldosterone antagonists, and alcohol disease are associated with hyponatremia. Treating hyponatremia may decrease the risk of fracture after low energy trauma. Therefore, physicians of different specialties should focus on treatment of chronic hyponatremia to reduce the fracture rate associated with low energy trauma., Competing Interests: None., (© 2019 The Authors.)

Objective: Investigation of the treatment of femur fractures and the type of femur fracture-associated complications regarding timing of surgery and length of hospital stay., Methods: In this retrospective cohort study, a total of 358 hip fractures were evaluated retrospectively from 1 January 2008 until 31 December 2010 at a level I trauma center in Germany. Inclusion criteria was age >18 years and a proximal femur fracture. Both sexes were evaluated. Mean age was 75.5 years, most patients were female (63.7%). Intervention was the operative treatment of proximal femur fracture. Outcome parameters were time until surgery, complications, reoperations, mortality, and length of hospital stay., Results: Among the proximal femur fractures (n = 358), 46.6% were pertrochanteric, 11.2% subtrochanteric, and 42.2% femoral neck fractures. Operation upon hip fractures was managed regularly within 24 hours of injury (73%; mean for femoral neck: 28.3 hrs.; mean for pertrochanteric fractures: 21.4 hrs.; mean for subtrochanteric fractures: 19.5 hrs.). Delayed treatment, as well as implantation of hip total endoprosthesis (TEP), increased the overall length of hospital stay (15.4 vs 17.6 days; 18.1 vs 15.8 days). Accordingly, surgical procedures performed within 24 hours of injury resulted in a shorter hospital residence. Longest delay of operation was measured for hip fractures (28.3 hrs.). In 351 patients, secondary injuries were detected in 94 individuals (26%), with fractures being the most common secondary injury (n = 40). We recorded postoperative complications of nonsurgical and surgical origin, and 33.6% of our patient cohort displayed complications. Complications were distributed among 118 patients. There was no significant difference in complications regarding the time of operation, with most nonsurgical and surgical complications appearing within 24 hours after operation (n = 110 vs n = 31). Nonsurgical complications, such as anemia (n = 49) and electrolyte imbalances (n = 30), were observed more frequently than surgical complications (n = 107 vs n = 34); however, these complications were reduced by delay in surgery (82.0% in 6-24 hrs. vs 74.2% in ≥24 hrs.). Anticoagulant therapy and age did not affect postoperative complications. The hospital mortality of patients was 6.2%. Follow-up was restrained to ambulatory visits in the clinic., Conclusions: Surgical management of hip fractures performed within 24 hours of injury minimizes hospital stay. We did not detect significant differences in the spectrum or number of complications regarding delay of surgery. Surgical complications mainly occur with rapid primary care, and medical complications can be reduced by more intensive preparation of patient and operation procedures., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Bisphosphonate alendronate (ALN), phytoestrogen 8-prenylnaringenin (8-PN) and the whole body vibration exert a favorable effect on osteoporotic bone. However, the impact of these treatments and the combination of pharmacological therapies with biomechanical stimulation on muscle and bone has not yet been explored in detail. The effect of ALN and 8-PN and their combination with the vibration (Vib) on skeletal muscle and bone healing was investigated in ovariectomized (Ovx) rats. Three-month old rats were Ovx ( n  = 78), or left intact (Non-Ovx; n  = 12). Five weeks after Ovx, all rats were treated according to the group assignment (n = 12/13): 1) Non-Ovx; 2) Ovx; 3) Ovx + Vib; 4) Ovx + ALN; 5) Ovx + ALN + Vib; 6): Ovx + 8-PN; 7) Ovx + 8-PN + Vib. Treatments with ALN (0.58 mg/kg BW, in food), 8-PN (1.77 mg/kg BW, daily s.c. injections) and/or with vertical vibration (0.5 mm, 35 Hz, 1 g , 15 min, 2×/day, 5×/week) were conducted for ten weeks. Nine weeks after Ovx, all rats underwent bilateral tibia osteotomy with plate osteosynthesis and were sacrificed six weeks later. Vibration increased fiber size and capillary density in muscle, enlarged callus area and width, and decreased callus density in tibia, and elevated alkaline phosphatase in serum. ALN and ALN + Vib enhanced capillarization and lactate dehydrogenase activity in muscle. In tibia, ALN slowed bone healing, ALN + Vib increased callus width and density, enhanced callus formation rate and expression of osteogenic genes. 8-PN and 8-PN + Vib decreased fiber size and increased capillary density in muscle; callus density and cortical width were reduced in tibia. Vibration worsened 8-PN effect on bone healing decreasing the callus width and area. Our data suggest that Vib, ALN, 8-PN, or 8-PN + Vib do not appear to aid bone healing. ALN + Vib improved bone healing; however application is questionable since single treatments impaired bone healing. Muscle responds to the anti-osteoporosis treatments and should be included in the evaluation of the drugs.

Objective: The posterior vertebral column resection (PVCR) comprises a one-step resection of the vertebral body by a costotransversectomy together with a 360° spondylodesis. After removing the vertebral body, straightening of the existing kyphotic malposition is possible., Indications: Pronounced thoracic kyphosis after osteoporotic sintering fractures in one or more vertebral bodies., Contraindications: General contraindications for surgical procedures, ASA >3 (American Society of Anesthesiologists)., Surgical Technique: First, dorsal stabilization of the vertebral column on at least two levels cranial and caudal of the VCR. Next, in a one-step procedure the laminectomy with costotransversectomy and the resection of the vertebral body is done. The ventral defect gap is filled by a mesh cage to provide ventral support. By compression the malposition is reduced and the mesh cage is fixed into position. Finally the vertebrae joints are opened up using a chisel and bone or bone substitute is placed to complete the 360° spondylodesis., Postoperative Management: Functional treatment without peak load exercises as well as appropriate osteoporosis treatment., Results: In a retrospective study 10 patients treated with this surgical technique were investigated. The results show a very good correction of the kyphotic maldeformity while the complications remain moderate.

Objective: Stabilization of the atlantoaxial transition by an alternative screw position in C1., Indications: Instabilities C1/C2 due to inflammation, tumor or trauma., Contraindications: Presence of a very small pedicle of C1. Variations in the course of the vertebral arteries., Surgical Technique: The midline approach to the upper cervical spine is used for the modified instrumentation of C1 with pedicle screws instead of Harms screws and for the unaltered instrumentation of C2. Depending on the indication, dorsal spondylodesis is performed by opening the laminae and attaching ceramic bone substitute material., Postoperative Management: In mobile patients, additional immobilisation with a soft collar is recommended for 6 weeks. Full recovery is given 3-4 months after surgery., Results: From January 2017 to September 2018, 21 stabilizations of the atlantoaxial transition were performed. The mean age was 72.52 ± 15.45 years. A total of 42 screws were placed in C1. In all, 21 (50%) C1 pedicle screwscould be placed, and in other 21 cases Harms screws were used. Complications were seen in 3 patients. Overall, considering the contraindications, the instrumentation of C1 with pedicle screws appears as a safe alternative to instrumentation with Harms screws.

Objective: The aim of the surgery is to restore the sagittal profile in the event of a mismatch of the patient's spinopelvic parameters and high patient suffering., Indications: Clinically symptomatic sagittal imbalance due to degeneration, trauma or after spinal surgery which can not be adequately treated by conservative therapy., Contraindications: Severe general disease of the patient; local or systemic inflammation., Surgical Technique: A dorsal approach is used to resect the dorsal vertebral structures and to perform an osteotomy to the anterior edge of the spine., Postoperative Management: Rest with a load limit of 5 kg for 3 months. Prohibition of deep sitting for this time., Results: The pedicle subtraction osteotomy is described in the literature as a reliable method for the treatment of sagittal imbalance. The high rate of described complications should be discussed preoperatively with the patient.

Objective: Operative stabilisation of osteoporotic vertebral fractures., Indications: Fractures of the thoracic and lumbar spine., Contraindications: None., Surgical Technique: Preoperative determination of expected bone mineral density. Implantation of pedicle screws in special trajectories, cement augmentation of the screws and use of alternative implants., Postoperative Management: Early functional mobilisation and initiation of osteoporosis therapy if indicated., Results: A biomechanical cadaver study with human vertebral bodies was performed. There was a highly significant correlation between bone mineral density and the fatigue load (r 2  = 0.839, p < 0.001). Specimens with bone mineral density below 80 mg/cm 3 only reached 60% of the fatigue load compared to the specimens with adequate bone quality (>120 mg/cm 3 ) and therefore stability mightbe insufficient and an additional stabilisation should be considered. In osteoporotic vertebrae, the fatigue strength of cement augmented screws was increased by 52% compared to the non-augmented screws (fatigue load non-augmented: 173 N, augmented: 263 N; p = 0.001). Studies conducted by other research groups have demonstrated the effect of various screw trajectories and alternative implants to improve stability in the treatment of osteoporotic vertebral body fractures.

Objective: Intraoperative revision of initially loosened pedicle screws., Indications: Intraoperatively loosened/stripped pedicle screws., Contraindications: None., Surgical Technique: Removal of the loosened/stripped pedicle screw. Checking the screw channel and re-implantation using a different trajectory, a larger screw diameter or a cement-augmented pedicle screw., Postoperative Management: Early functional mobilization and initiation of osteoporosis therapy if indicated., Results: A biomechanical study with human vertebral bodies was performed. Augmented and not augmented pedicle screws were tested until loosening using a fatigue testing setup. After loosening occurred a subsequent augmentation of the loosened, not augmented screw was performed, and it was tested using a fatigue test again. Both the initial (p = 0.009) and the augmentation after loosening (p = 0.001) showed a significant increase in failure load compared to the non-augmented pedicle screws. In our own patient collective from April 2016 to August 2018, 11 of 524 patients treated with pedicle screws showed intraoperative screw loosening. This was revised in 6 cases with a subsequent augmentation and in 5 cases with a larger screw diameter. In the postoperative control at 6 weeks, none of these screws showed loosening again.

Objective: In aging population, postmenopausal osteoporosis and decline of musculoskeletal function, referred to as "frailty syndrome" lead to loss of bone and muscle, causing falls, and fall-related injuries. To limit the impact of this portentous duo, simultaneous treatment of both is needed. Urocortin (UCN) has been reported to improve osteoporotic bone properties while its effect on muscle has not been addressed yet. Design and Methods: We aimed to investigate the effect of urocortin in vivo on skeletal muscle structure in osteopenic rats. Sixty Sprague-Dawley rats were divided into five groups: four were ovariectomized (OVX) and one underwent sham operation (SHAM). One ovariectomized group was left untreated (OVX), while one was treated with urocortin s.c. in 3 μg/kg body weight (bw) (OVX+UCN low), one with 30 μg/kg (OVX+UCN high), while one group was treated with estradiol orally (OVX+E: 0.2 mg/kg bw), each for 35 days. Mm. gastrocnemius, longissimus , and soleus were isolated and capillary density as well as diameters of type I and II fibers were measured. In addition, we examined the effect of UCN on tibia using biomechanical, micro-CT and ashing analysis and investigated the blood serum. Results: We demonstrated a positive effect of UCN on M. soleus , in which fiber diameter was positively influenced. The biomechanical and structural parameters of bone were not changed in UCN treated rats. The higher cholesterol, glucose and triglyceride levels in the "UCN high" group raise concern about this treatment. Conclusions: Our results portray urocortin as a substance that can be assessed for future therapeutic treatments of estrogen deficiency. New and Noteworthy: Urocortin has a positive effect on M. soleus (diameter). Urocortin raises serum cholesterol and triglyceride levels. Bone tissue was not affected by UCN.

Selective androgen receptor modulators (SARMs) have shown beneficial effects on muscle wasting, general physical function and bone properties in male mammals. However, data on the effects of SARMs in postmenopausal osteoporotic bone are scarce. We evaluated the effects of the SARM drug ostarine on postmenopausal osteoporotic bone in a rat osteoporosis model. Ovariectomy was performed on 46 of 56 3-month-old female Sprague-Dawley rats. Eight weeks after ovariectomy, ostarine was orally administered daily for 5 weeks in dosages of 0.04 (low, OVX + Ost. 0.04), 0.4 (intermediate, OVX + Ost. 0.4), and 4 mg/kg (high, OVX + Ost. 4) body weight. Another ovariectomized group received no ostarine. Lumbar vertebrae and femora were removed for biomechanical, gene expression, ashing, and computer tomography analyses. Low dose showed no effects. The effects of intermediate and high doses were comparable overall. Improvements were mainly seen in structural properties such as bone mineral density and bone volume density. However, the effects in femora were superior to effects in vertebrae. Ostarine treatment for 5 weeks did not improve significantly biomechanical properties. mRNA expression of the receptor activator of NF-κB ligand decreased after treatment, and uterine weight increased. Serum levels of phosphorus increased following ostarine treatment in intermediate and high-dose groups. Short-term treatment of osteoporotic bone with ostarine leads to improvement of several microstructural bone indices. While we did not observe changes in biomechanics, it is conceivable that longer treatment may also improve biomechanical properties. Further studies are needed to characterize longer time effects and side effects of ostarine in osteoporosis.

Background: Osteoporosis is one of the world's major medical burdens in the twenty-first century. Pharmaceutical intervention currently focusses on decelerating bone loss, but phytochemicals such as baicalein, which is a lipoxygenase inhibitor, may rescue bone loss. Studies evaluating the effect of baicalein in vivo are rare., Methods: We administered baicalein to sixty-one three-month-old female Sprague-Dawley rats. They were divided into five groups, four of which were ovariectomized (OVX) and one non-ovariectomized (NON-OVX). Eight weeks after ovariectomy, bilateral tibial osteotomy with plate osteosynthesis was performed and bone formation quantified. Baicalein was administered subcutaneously using three doses (C1: 1 mg/kg BW; C2: 10 mg/kg BW; and C3: 100 mg/kg BW) eight weeks after ovariectomy for four weeks. Finally, femora and tibiae were collected. Biomechanical tests, micro-CT, ashing, histological and gene expression analyses were performed., Results: Biomechanical properties were unchanged in tibiae and reduced in femora. In tibiae, C1 treatment enhanced callus density and cortical width and decreased callus area. In the C3 group, callus formation was reduced during the first 3 weeks after osteotomy, correlating to a higher mRNA expression of Osteocalcin , Tartrate-resistant acid phosphatase and Rankl . In femora, baicalein treatments did not alter bone parameters., Conclusions: Baicalein enhanced callus density and cortical width but impaired early callus formation in tibiae. In femora, it diminished the biomechanical properties and calcium-to-phosphate ratio. Thus, it is not advisable to apply baicalein to treat early bone fractures. To determine the exact effects on bone healing, further studies in which baicalein treatments are started at different stages of healing are needed., Competing Interests: The local ethics committee permitted the experiment (application number G14/1530).Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: The treatment of severely injured patients in the trauma resuscitation unit (TRU) requires an interdisciplinary and highly professional trauma team approach. The complete team needs to be waiting for the patient in the TRU on arrival. Treating severely injured patients in the TRU, the trauma team connects the initial preclinical emergency stabilization with the subsequent sophisticated treatment. Thus, the trauma team depends on concise information from the emergency personnel at the scene to provide its leader with further information as well as an accurate alarm including all departments necessary to stabilize the patient in the TRU., Method: Aiming at an accurate and most efficient trauma team alarm, this study was designed to provide and analyze an alarm system which mobilizes the trauma team in a stepwise fashion depending on the pattern of injuries and the threat to life. The trauma team alarm system was analyzed in a prospective data acquisition at a level I trauma center over a period of 12 months. Evaluation followed the acquisition phase and provided comparison to the status prior to the establishment of the alarm system. All items underwent statistical testing using t‑tests (p < 0.05)., Results: The data of 775 TRU patients showed a significant reduction of false information on the patients status prior to arrival. It also showed an increase in punctual arrival in the TRU of the emergency teams. False alarms were significantly reduced (from 11.9% to 2.7%, p > 0.01). The duration from arrival of the patient in the TRU to the initial multislice computed tomography (CT) scan was reduced by 6 min while the total period of treatment in the TRU was reduced by 17 min. After the alarm system to gradually mobilize the trauma team was put into action, team members left the TRU if unneeded prior to finishing the initial treatment in only 4% of the cases. The patient fatality rate was 8.8% (injury severity score, ISS = 23 points) after establishment of the alarm system compared to 12.9% (ISS = 25 points) before., Conclusion: The implementation of an accurate and patient status-based alarm system to mobilize the trauma team can improve the quality of treatment while the duration of treatment of the severely injured patients in the TRU can be decreased. It also provides a most efficient mobilization of personnel resources while sustaining patient safety.

Rebalancing of the RANKL/OPG system seems to be an effective treatment strategy in postmenopausal osteoporosis. Here, we evaluate the knockdown of RANKL by in-vivo-delivered siRNA in a rat model of osteoporosis. Virus-like-particles (VLPs) derived from polyoma JC virus were used for delivering RANKL siRNA in ovariectomized (OVX) rats. 48 rats were ovariectomized and treated with either 17β-estradiol (E2), VLPs containing RANKL siRNA (siRANKL), or VLPs containing non-cognate siRNA (siCtrl). All OVX groups were subdivided into the prophylaxis group (PG) and the therapy group (TG). The PG received treatment directly after being OVX for 10 weeks. The TG received treatment 5 weeks after being OVX for 5 weeks. Rats were sacrificed 10 weeks after being OVX. Bone and blood samples were analyzed. E2 and siRANKL showed a significant knockdown of RANKL mRNA. A protein knockdown was observed with E2 and siRANKL in the TG but not in the PG. No distinct improvements in biomechanical and morphological properties of the bones were observed after siRANKL treatment. In the PG, E2 protected the bone structure. We demonstrated successful mRNA and protein knockdown by VLP-mediated RNAi in vivo. Knockdown of membranous RANKL did not result in significant improvements of bone properties in this model of early-stage postmenopausal osteoporosis., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Reduction of femoral shaft fractures remains a challenging problem in orthopaedic surgery. Robot-assisted reduction might ease reduction and fracture treatment. However, the influence of different reduction pathways on patients' physiology is not fully known yet. Therefore, the aim of this study was to examine the biomechanics and histology of fracture healing after direct and prolonged robot-assisted reduction in an in vivo rat model., Methods: 144 male CD ® rats were randomly assigned to 12 groups. Each animal received an external fixator and an osteotomy on the left femoral shaft. On the fourth postoperative day, the 1× reduction groups received a single reduction maneuver, whereas the 10× reduction groups received the same reduction pathway with ten repetitions. The control groups did not undergo any reduction maneuvers. Animals were killed after 1, 2, 3 and 4 weeks, respectively, and the composition of the fracture gap was analyzed by µCT and non-decalcified histology. Biomechanical properties were investigated by a three-point bending test, and the bone turnover markers PINP, bCTx, OPG, sRANKL, TRACP-5b, BALP, and OT/BGP were measured., Results: One week after the reduction maneuver, µCT analysis showed a higher cortical bone volume in the 1× reduction group compared to the 10× reduction group. Biomechanically, the control group showed higher maximum force values measured by three-point bending test compared to both reduction groups. Furthermore, less collagen I formation was examined in the 10× reduction group compared to the control group after 1 week of fracture healing. PINP concentration was decreased in 10× reduction group after 1 week compared to control group. The same trend was seen after 3 weeks., Conclusion: A single reduction maneuver has a beneficial effect in the early phase of the fracture healing process compared to repeated reduction maneuvers. In the later phase of fracture healing, no differences were found between the groups.

Most models of osteoporotic bone fractures are performed unilaterally (UL). We investigated healing of tibia osteotomy performed either UL or bilaterally (BL) in ovariectomized rats. Behavior of animals and muscle structure were assessed. Three-month-old female Sprague-Dawley rats were ovariectomized (n = 32). After 10 weeks, half the rats underwent UL osteotomy of tibia metaphysis (right limb) with plate osteosynthesis. The other rats were osteotomized BL. Half of the rats in each group received either standard pain treatment with carprofen (5 mg/kg body weight (BW), 1x/day for 2 days) or carprofen and buprenorphine (5 mg/kg BW, 1x/day and 0.03 mg/kg BW, 2x/day for 5 days) after osteotomy. The UL rats started to load the injured limb from day 27 ± 9; BL rats did this from day 4 ± 4 onward. The UL rats more frequently loaded only one hind limb; BL rats more often loaded both hind limbs. Osteotomy was not bridged in 20% of UL rats and in 4% of BL rats. Callus volume and bone volume fraction were lower in UL group. Weight and fiber size of UL-intact limb muscles were enhanced, compared to the osteotomized limb and those in BL group. Most of the other parameters which assess physiology, activity, body posture, head, or coat were not different. The effect of two pain therapies was not significant on any variable studied. Welfare of the animals was acceptable in all rats. In UL rats, bone healing was delayed. The more advanced healing in BL rats suggested a positive effect of earlier loading. In studies on bone healing, it is advisable to perform BL osteotomy.

Osteoporosis is often accompanied by sarcopenia. The effect of strontium ranelate (SR) on muscle tissue has not been investigated sufficiently. In this study, the effect of different SR treatments on muscle was studied. Additionally, the lumbar vertebrae were analyzed. Three-month-old female rats were divided into five groups (n = 12): Group 1: untreated (NON-OVX); Group 2: ovariectomized and left untreated (OVX); Group 3: SR after OVX until the study ended (13 weeks, SR prophylaxis and therapy = pr+th); Group 4: OVX and SR for 8 weeks (SR prophylaxis = pr); Group 5: SR for 5 weeks from the 8 week after OVX (SR therapy = SR th). SR was applied in food (630 mg/kg body weight). The size of muscle fibers, capillary density, metabolic enzymes, and mRNA expression were assessed in soleus, gastrocnemius, and longissimus muscles. The vertebral bodies underwent micro-CT, biomechanical, and ashing analyses. In general, SR did not alter the muscle histological parameters. The changes in fiber size and capillary ratio were related to the body weight. Myostatin mRNA was decreased in Sr pr+th; protein expression was not changed. SR th led to increase in mRNA expression of vascular endothelial growth factor (Vegf-B). In lumbar spine, SR pr+th enhanced biomechanical properties, bone mineral density, trabecular area, density, and thickness and cortical density. The reduced calcium/phosphate ratio in the SR pr+th group indicates the replacement of calcium by strontium ions. SR has no adverse effects on muscle tissue and it shows a favorable time-dependent effect on vertebrae. A functional analysis of muscles could verify these findings.

Estrogen deficiency and aging are associated with osteoporosis, impaired bone healing, and lower cognitive performance. Close functional and physical connections occur between bone and the central nervous system. An anti-inflammatory drug, zileuton (which is an inhibitor of arachidonate 5-lipoxygenase), is known to have a positive effect on bone tissue repair and brain ischemia. We studied the effect of zileuton on osteopenic bone and its healing and on the genes considered to be crucial for the cross talks between bone and brain. Three-month-old Sprague-Dawley rats were ovariectomized or left untreated. After 8 wk, bilateral metaphyseal tibia osteotomy with plate osteosynthesis was performed in all rats. Ovariectomized rats were fed with food containing zileuton (1, 10, or 100 mg/kg body wt) for 5 wk. In tibiae, bone volume, callus and cortical volume, and gene expression of osteocalcin and alkaline phosphatase were enhanced by zileuton (10 or 100 mg); biomechanical properties and bone density were not changed. In femur, zileuton enlarged cortical volume distal and trabecular volume proximal, decreasing their density. The expression level of brain Sema3a, known to regulate bone mass positively, was downregulated after ovariectomy. In contrast, bone Sema4d, a negative regulator of bone mass, was upregulated in the tibia callus after ovariectomy, whereas zileuton treatment (10 or 100 mg) resulted in reverse effects. Here, we describe for the first time the expression of Rbbp4 mRNA and its increase in tibia after ovariectomy. Zileuton caused downregulation of Rbbp4 in the hippocampus and had an effect on bone healing, changed the expression of genes involved in cross talk between bones and brain, and may be a potent drug for further examination in estrogen deficiency-related dysfunction(s). NEW & NOTEWORTHY Zileuton, a 5-lipoxygenase inhibitor, increased bone volume, callus and cortical volume in osteotomized tibia, and trabecular and cortical volume in femur. Although the expression of Sema3a (positively regulating bone mass) in brain was downregulated and Sema4d (negatively regulating bone mass) was upregulated in tibia callus after ovariectomy, zileuton could counteract these effects. Rbbp4 (involved in age-related memory loss) was increased in tibia callus after ovariectomy.

Osteoporosis is one of the most common diseases worldwide. In osteoporosis, vertebral fractures represent a major burden. Lipoxygenase (LOX) inhibitors such as baicalein and zileuton may represent a promising therapeutic option owing to their antioxidative effects and suppression of various inflammatory processes in muscle and bone. The effect of these LOX inhibitors on the spine was studied in osteopenic rats. Female Sprague-Dawley rats were divided two times into five groups: four groups each were ovariectomized (OVX) and one control group was non-ovariectomized (NON-OVX). Eight weeks after ovariectomy, three concentrations of baicalein (1mg/kg body weight [BW], 10mg/kgBW, and 100mg/kgBW) were administered subcutaneously daily in three OVX groups for 4weeks. Similarly, zileuton was administered in three concentrations via food for 5weeks. In vivo computed tomography (pQCT) of the spine was performed before the treatments and at the end of the experiment. Lumbar vertebrae were subjected to a compression test, micro-CT, and ashing analyses. After baicalein treatment, cortical bone mineral density (BMD) was improved; trabecular connectivity and trabecular BMD were diminished at high dose. After zileuton treatment, the total BMD, anorganic weight, trabecular nodes, and trabecular area were improved. The in vivo stress-strain index was increased and alkaline phosphatase activity in serum was enhanced after both treatments. A dose-dependent effect was not clearly observed after both treatments. The treatments using baicalein for 4 and zileuton for 5weeks were not sufficient to change the biomechanical properties and bone volume fraction (BV/TV). Overall, baicalein improved the cortical bone parameters whereas zileuton had a favorable effect on the trabecular structure. Moreover, both treatments increased the bone formation rate. Longer trials, a combination of both LOX inhibitors, and their effect at the cellular and molecular levels should be investigated in further studies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The consequences of traumatic brain injury (TBI) for health-related quality of life (HRQoL) are still poorly understood, and no TBI-specific instrument has hitherto been available. This paper describes in detail the psychometrics and validity of the German version of an internationally developed, self-rated HRQoL tool after TBI-the QOLIBRI (Quality of Life after Brain Injury). Factors associated with HRQoL, such as the impact of cognitive status and awareness, are specifically reported. One-hundred seventy-two participants after TBI were recruited from the records of acute clinics, most of whom having a Glasgow Coma Scale (GCS) 24-hour worst score and a Glasgow Outcome Scale (GOSE) score. Participants had severe (24%), moderate (11%) and mild (56%) injuries as assessed on the GCS, 3 months to 15 years post-injury. The QOLIBRI uses 37 items to measure "satisfaction" in the areas of "Cognition", "Self", "Daily Life and Autonomy", and "Social Relationships", and "feeling bothered" by "Emotions"and "Physical Problems". The scales meet standard psychometric criteria (α = .84 to .96; intra-class correlation-ICC = .72 to .91). ICCs (0.68 to 0.90) and αs (.83 to .96) were also good in a subgroup of participants with lower cognitive performance. The six-subscale structure of the international sample was reproduced for the German version using confirmatory factor analyses and Rasch analysis. Scale validity was supported by systematic relationships observed between the QOLIBRI and the GOSE, Patient Competency Rating Scale for Neurorehabilitation (PCRS-NR), Hospital Anxiety and Depression Scale (HADS), Profile of Mood States (POMS), Short Form 36 (SF-36), and Satisfaction with Life Scale (SWLS). The German QOLIBRI contains novel information not provided by other currently available measures and has good psychometric criteria. It is potentially useful for clinicians and researchers, in post-acute and rehabilitation studies, on a group and individual level.

We investigated the combinatorial effects of whole-body vertical vibration (WBVV) with the primarily osteoanabolic parathyroid hormone (PTH) and the mainly antiresorptive strontium ranelate (SR) in a rat model of osteoporosis. Ovariectomies were performed on 76 three-month-old Sprague-Dawley rats (OVX, n = 76; NON-OVX, n = 12). After 8 weeks, the ovariectomized rats were divided into 6 groups. One group (OVX + PTH) received daily injections of PTH (40 µg/kg body weight/day) for 6 weeks. Another group (OVX + SR) was fed SR-supplemented chow (600 mg/kg body weight/day). Three groups (OVX + VIB, OVX + PTH + VIB, and OVX + SR + VIB) were treated with WBVV twice a day at 70 Hz for 15 min. Two groups (OVX + PTH + VIB, OVX + SR + VIB) were treated additionally with PTH and SR, respectively. The rats were killed at 14 weeks post-ovariectomy. The lumbar vertebrae and femora were removed for biomechanical and morphological assessment. PTH produced statistically significant improvements in biomechanical and structural properties, including bone mineral density (BMD) and trabecular bone quality. In contrast, SR treatment exerted mild effects, with significant effects in cortical thickness only. SR produced no significant improvement in biomechanical properties. WBVV as a single or an adjunctive therapy produced no significant improvements. In conclusion, vibration therapy administered as a single or dual treatment had no significant impact on bones affected by osteoporosis. PTH considerably improved bone quality in osteoporosis cases and is superior to treatment with SR.

Background: Due to restrictions on admission to medical school, changing claims to an optimized work-life balance and occupational perspectives, surgical professions in particular are struggling with strategies to motivate young academics. Surgical disziplines aim towards a profound transfer of knowledge and pique student's interest by ensuring a sustainable education at university., Objectives: The goal of this study was to evaluate a Students-On-Call System (SOCS) and to identify a financial benefit., Materials and Methods: In this study the SOCS was compared pre-/postevaluation using questionnaires and the supporting X‑rays within a curricular teaching module of orthopedic trauma surgery, with students in the fourth semester of specialism and those in the practical semester at medical school., Results: The students of SOCS showed significantly better results prior to the course and afterwards than the two other groups. By establishing SOCS medical students get involved into the treatment of emergency patients in the trauma resuscitation unit (TRU) and operating room (OR). Students get the chance to enhance their comprehension of diagnostics, therapy and decision making in surgical context. This highly valuable traineeship combines a minimized teaching effort with an effective motivation of young academcis for the surgical profession. A SOCS has reduced the workload of medical colleagues. Establishing SOCS spare the residents being on call and results in reduced costs of 23,659.86 Euro per year., Conclusion: The results presented show that the SOCS leads to an excellent cost-benefit balance, which has been established in multiple surgical departments at the medical school of the University of Göttingen. Apart from practice-oriented surgical teaching, the SOCS is a way of promoting successful young talent saving resources in the medical on-call services.

The aim of the present study was to study the effect of combined therapy of teriparatide (PTH) or strontium ranelate (SR) with whole-body vibration (WBV) on bone healing and muscle properties in an osteopenic rat model. Seventy-two rats (3 months old) were bilaterally ovariectomized (Ovx), and 12 rats were left intact (Non-Ovx). After 8 weeks, bilateral transverse osteotomy was performed at the tibia metaphysis in all rats. Thereafter, Ovx rats were divided into six groups (n = 12): (1) Ovx-no treatment, (2) Ovx + vibration (Vib), (3) SR, (4) SR + Vib, (5) PTH, and (6) PTH + Vib. PTH (40 μg/kg BW sc. 5×/week) and SR (613 mg/kg BW in food daily) were applied on the day of ovariectomy, vibration treatments 5 days later (vertical, 70 Hz, 0.5 mm, 2×/day for 15 min) for up to 6 weeks. In the WBV + SR group, the callus density, trabecular number, and Alp and Oc gene expression were decreased compared to SR alone. In the WBV + PTH group, the cortical and callus widths, biomechanical properties, Opg gene expression, and Opg/Rankl ratio were increased; the cortical and callus densities were decreased compared to PTH alone. A case of non-bridging was found in both vibrated groups. Vibration alone did not change the bone parameters; PTH possessed a stronger effect than SR therapy. In muscles, combined therapies improved the fiber size of Ovx rats. WBV could be applied alone or in combination with anti-osteoporosis drug therapy to improve muscle tissue. However, in patients with fractures, anti-osteoporosis treatments and the application of vibration could have an adverse effect on bone healing.

Bone remodeling requires a precise balance between formation and resorption. This complex process involves numerous factors that orchestrate a multitude of biochemical events. Among these factors are hormones, growth factors, vitamins, cytokines, and, most notably, osteoprotegerin (OPG) and the receptor activator for nuclear factor-kappaB ligand (RANKL). Inflammatory cytokines play a major role in shifting the RANKL/OPG balance toward excessive RANKL, resulting in osteoclastogenesis, which in turn initiates bone resorption, which is frequently associated with osteoporosis. Rebalancing RANKL/OPG levels may be achieved through either upregulation of OPG or through transient silencing of RANKL by means of RNA interference. Here, we describe the utilization of a viral capsid-based delivery system for in vivo and in vitro RNAi using synthetic small interfering RNA (siRNA) molecules in rat osteoblasts. Polyoma JC virus-derived virus-like particles are capable of delivering siRNAs to target RANKL in osteoblast cells both in vitro and in a rat in vivo system. Expression levels were monitored using quantitative real-time polymerase reaction and enzyme-linked immunosorbent assay after single and repeated injections over a 14-day period. Our data indicate that this is an efficient and safe route for in vivo delivery of gene modulatory tools to study important molecular factors in a rat osteoporosis model.

Sarcopenia, a loss of muscle mass accompanying osteoporosis, leads to falls and fall-related injuries. Baicalein, as a phytochemical agent, has an antioxidative and anti-inflammatory effect in muscle. In this study, sixty-one female Sprague Dawley rats were divided into five groups: four groups were ovariectomized (OVX) and one control group was nonovariectomized (NON-OVX). Eight weeks after ovariectomy, three disparate concentrations (1 mg/kg body weight (BW), 10 mg/kg BW, and 100 mg/kg BW) of baicalein were applied subcutaneously daily in three OVX groups. Mm. soleus, gastrocnemius, and longissimus were extracted; their diameter, area, relation to body, and muscle weights as well as number of capillaries per fibre were recorded. In Mm. soleus and gastrocnemius, the baicalein effect (increasing number of capillaries per fibre) was proportional to the dose applied. The fibre diameters and area under baicalein treatment were significantly greater compared to OVX and NON-OVX groups. In M. longissimus, we observed a shift to type IIa fibres. Serum creatine kinase levels were significantly lower in highest baicalein concentration group. We conclude that baicalein can stimulate angiogenesis, though not fibre type-specific, in skeletal muscle and reduce the estrogen-related loss of fibre diameter and area in the skeletal muscle in rats. Therefore, a protective effect of baicalein on muscle cells can be assumed., Competing Interests: The authors declare that they have no competing interests.

Background. 8-Prenylnaringenin (8-PN) is the phytoestrogen with the highest affinity for estrogen receptor-α (ER-α), which is required to maintain BMD. The osteoprotective properties of 8-PN have been demonstrated previously in tibiae. We used a rat osteopenia model to perform the first investigation of 8-PN with whole-body vertical vibration (WBVV). Study Design. Ovariectomy was performed on 52 of 64 Sprague-Dawley rats. Five weeks after ovariectomy, one group received daily injections (sc) of 8-PN (1.77 mg/kg) for 10 weeks; a second group was treated with both 8-PN and WBVV (twice a day, 15 min, 35 Hz, amplitude 0.47 mm). Other groups received either only WBVV or no treatment. Methods. The rats were sacrificed 15 weeks after ovariectomy. Lumbar vertebrae and femora were removed for biomechanical and morphological assessment. Results. 8-PN at a cancer-safe dose did not cause fundamental improvements in osteoporotic bones. Treatment with 8-PN caused a slight increase in uterine wet weight. Combined therapy using WBVV and 8-PN showed no significant improvements in bone structure and biomechanical properties. Conclusion. We cannot confirm the osteoprotective effects of 8-PN at a cancer-safe dose in primary affected osteoporotic bones. Higher concentrations of 8-PN are not advisable for safety reasons. Adjunctive therapy with WBVV demonstrates no convincing effects on bones.

The following questions were addressed: whether therapy with strontium ranelate (SR) should be continued or interrupted if the fractures occur during SR treatment and whether SR could be applied directly after fracture to improve bone healing. Sprague-Dawley rats (3 month old) were ovariectomized (Ovx, n = 48) or left intact (n = 12). After 8 weeks, a bilateral transverse osteotomy of the tibia metaphysis was created in all rats. Ovx rats were divided into four groups: Ovx; SR applied directly after Ovx until osteotomy (prophylaxis, SR pr, 8 weeks); SR applied after osteotomy (therapy, SR th, 5 weeks); SR applied during the whole experiment (pr + th, 13 weeks). SR dosage was 625 mg/kg body weight/day, administered in the feed. Five weeks later, tibiae were analyzed by biomechanical, histological, micro-CT, and gene expression analyses. The SR pr + th treatment increased total bone mineral density (BMD), bone volume fraction, cortical BMD and volume, callus area and density, serum alkaline phosphatase, tartrate-resistant acid phosphatase mRNA, accelerated osteotomy bridging, and callus formation at weeks 2 and 3 of healing and decreased the osteoprotegerin/receptor activator of nuclear factor kB ligand mRNA ratio. SR th enlarged callus area and improved callus formation during the 5th week of healing. SR pr improved cortical BMD preserving bone after SR discontinuation (5-week rest); the bone healing was not affected. SR content in the tibia metaphysis was the highest in SR pr + th group and was not different between SR pr and SR th. SR has a positive effect on osteoporotic bone healing in rat and SR treatment can be continued after the fracture occurs or applied directly after the fracture.

As yet there is no evidence of the potential antiosteoporotic effect of Urocortin-1 (UCN), a corticotropin releasing factor related peptide, in vivo. In this study, and for the first time, we investigated the effect of UCN in a rat osteopenia model. Sixty female Sprague-Dawley rats were divided into 5 groups: (1) sham-operated, (2) untreated ovariectomized (OVX) rats, (3) and (4) OVX animals treated for 5 weeks with daily subcutaneous low-dose UCN (3 μg/kg of BW) or high-dose UCN (30 μg/kg of BW) 8 weeks after ovariectomy, and (5) OVX rats treated with daily estrogen (0.2 mg/kg of BW p.o) 8 weeks after ovariectomy for 5 weeks (E). After sacrifice, the femurs were reserved for biomechanical, histomorphometric and ash testing. In the biomechanical test, the high-dose UCN rats showed significantly improved mechanical stiffness (341.6 N/mm) compared with the untreated OVX animals (275.9 N/mm). In the histomorphometric evaluation, the high-dose UCN rats demonstrated an improved trabecular microarchitecture especially and significantly at the distal femur (distal femur Tb.Ar = 41.4% and N.Nd/mm(2) = 26.8, proximal femur Tb.Ar = 71.8% and N.Nd/mm(2) = 28.7) compared with untreated OVX rats (distal femur Tb.Ar = 23.3% and N.Nd/mm(2) = 11.7, proximal femur Tb.Ar = 60.2% and N.Nd/mm(2) = 25.2). Our results show that short-term treatment with UCN seems to have a positive effect on the metaphyseal bone structure and strength of the femur in ovariectomized rats.