[Innovative noninvasive gait-synchronized vibrotactile feedback system : "I can feel myself walking again"]. / Innovatives nichtinvasives gangsynchrones vibrotaktiles Feedbacksystem : "Ich fühle, wie ich gehe".

Despite intensive research and development of systems for restoration of sensory information, these have so far only been the subject of study protocols. A new noninvasive feedback system translates pressure loads on the forefoot and hindfoot into gait-synchronized vibrotactile stimulation of a defined skin area. To increase the authenticity, this treatment can be supplemented by a surgical procedure. Targeted sensory reinnervation (TSR) describes a microsurgical procedure in which a defined skin area on the amputated stump of the residual limb is first denervated and then reinnervated by a specific, transposed sensory nerve harvested from the amputated part of the limb. This creates a sensory interface at the residual stump. This article presents the clinical and orthopedic technical treatment pathway with this innovative vibrotactile feedback system and explains in detail the surgical procedure of TSR after amputation of the lower limb.

[Osteoporotic vertebral fractures of the thoracic and lumbar spine]. / Osteoporotische Wirbelkörperfrakturen der Brust- und Lendenwirbelsäule.

The frequency of osteoporotic vertebral fractures in the clinical routine is increasing due to the demographic change. They are the most frequent fractures associated with osteoporosis and affect an especially morbid and vulnerable group of patients. These fractures often occur after minor trauma or spontaneously. Pain is the predominant symptom, whereas mechanical stability is mostly sufficient, in comparison to vertebral fractures after high-energy trauma, and is not a predominant indication for surgery. These fractures can be described using the classification for fractures associated with osteoporosis and the corresponding treatment recommendations are guided by them. Besides the specific treatment of osteoporotic vertebral fractures, a holistic treatment of patients taking pre-existing comorbidities into consideration is decisive. A mobilization as quickly as possible and treatment of the underlying osteoporosis are important to prevent further fractures.

[Comparison of planimetric CT­based volumetry with simplified models for determining the size of intrapelvic hematomas due to pelvic fractures in emergency room diagnostics]. / Vergleich von planimetrisch CT­gestützter Volumetrie mit vereinfachten Modellen zur Größenbestimmung intrapelviner Hämatome bei Beckenfrakturen im Rahmen der Schockraumdiagnostik.

BACKGROUND: Bleeding in the pelvis can lead to a circulatory problem. The widely used whole-body computed tomography (WBCT) scan in the context of treatment in the trauma resuscitation unit (TRU) can give an idea of the source of bleeding (arterial vs. venous/osseous); however, the volume determination of an intrapelvic hematoma by volumetric planimetry cannot be used for a quick estimation of the blood loss. Simplified measurement techniques using geometric models should be used to estimate the extent of bleeding complications. OBJECTIVE: To determine whether simplified geometric models can be used to quickly and reliably determine intrapelvic hematoma volume in fractures type Tile B/C during emergency room diagnostics or whether the time-consuming planimetric method must always be used. MATERIAL AND METHODS: Retrospectively, 42 intrapelvic hemorrhages after pelvic fractures Tile B + C (n = 8:B, 34:C) at two trauma centers in Germany were selected (66% men, 33% women; mean age 42 ± 20 years) and the CT scans obtained during the initial trauma scan were analyzed in more detail. The CT datasets of the included patients with 1-5 mm slice thickness were available for analysis. By area labelling (ROIs) of the hemorrhage areas in the individual slice images, the volume was calculated by CT volumetrically. Comparatively, volumes were calculated using simplified geometric figures (cuboid, ellipsoid, Kothari). A correction factor was determined by calculating the deviation of the volumes of the geometric models from the planimetrically determined hematoma size. RESULTS AND DISCUSSION: The median planimetric bleeding volume in the total collective was 1710 ml (10-7152 ml). Relevant pelvic bleeding with a total volume > 100 ml existed in 25 patients. In 42.86% the volume was overestimated in the cuboid model and in 13 cases (30.95%) there was a significant underestimation to the planimetrically measured volume. Thus, we excluded this volume model. In the models ellipsoid and measuring method according to Kothari, an approximation to the planimetrically determined volume could be achieved with a correction factor calculated via a multiple linear regression analysis. The time-saving and approximate quantification of the hematoma volume using a modified ellipsoidal calculation according to Kothari makes it possible to assess the extent of bleeding in the pelvis after trauma if there are signs of a C-problem. This measurement method, as a simple reproducible metric, could be embedded in trauma resuscitation units (TRU) in the future.

Advantage of ostarine over raloxifene and their combined treatments for muscle of estrogen-deficient rats.

PURPOSE: Selective androgen (ostarine, OST) and estrogen (raloxifene, RAL) receptor modulators with improved tissue selectivity have been developed as alternatives to hormone replacement therapy. We investigated the combined effects of OST and RAL on muscle tissue in an estrogen-deficient rat model of postmenopausal conditions. METHODS: Three-month-old Sprague Dawley rats were divided into groups: (1) untreated non-ovariectomized rats (Non-OVX), (2) untreated ovariectomized rats (OVX), (3) OVX rats treated with OST, (4) OVX rats treated with RAL, (5) OVX rats treated with OST and RAL. Both compounds were administered in the diet. The average dose received was 0.6 ± 0.1 mg for OST and 11.1 ± 1.2 mg for RAL per kg body weight/day. After thirteen weeks, rat activity, muscle weight, structure, gene expression, and serum markers were analyzed. RESULTS: OST increased muscle weight, capillary ratio, insulin-like growth factor 1 (Igf-1) expression, serum phosphorus, uterine weight. RAL decreased muscle weight, capillary ratio, food intake, serum calcium and increased Igf-1 and Myostatin expression, serum follicle stimulating hormone (FSH). OST + RAL increased muscle nucleus ratio, uterine weight, serum phosphorus, FSH and luteinizing hormone and decreased body and muscle weight, serum calcium. Neither treatment changed muscle fiber size. OVX increased body and muscle weight, decreased uterine weight, serum calcium and magnesium. CONCLUSION: OST had beneficial effects on muscle in OVX rats. Side effects of OST on the uterus and serum electrolytes should be considered before using it for therapeutic purposes. RAL and RAL + OST had less effect on muscle and showed endocrinological side effects on pituitary-gonadal axis.

Treatment of osteoporosis using a selective androgen receptor modulator ostarine in an orchiectomized rat model.

PURPOSE: The selective androgen receptor modulator ostarine has been shown to have advantageous effects on skeletal tissue properties, reducing muscle wasting and improving physical function in males. However, data on effects in male osteoporosis remain limited. In this study, the effects of ostarine on osteoporotic bone were evaluated in a rat model of male osteoporosis and compared with those of testosterone treatments. METHODS: Eight-month-old male Sprague-Dawley rats were either non-orchiectomized to serve as a healthy control (Non-Orx, Group 1) or orchiectomized (Orx, Groups 2-6) and then grouped (n = 15/group): (1) Non-Orx, (2) Orx, (3) Ostarine Therapy, (4) Testosterone Therapy, (5) Ostarine Prophylaxis and (6) Testosterone Prophylaxis. Prophylaxis treatments started directly after orchiectomy and continued for 18 weeks, whereas Therapy treatments were initiated 12 weeks after Orx. Ostarine and Testosterone were applied orally at daily doses of 0.4 and 50 mg/kg body weight, respectively. The lumbar vertebral bodies and femora were analyzed using biomechanical, micro-CT, ashing, and gene expression analyses. RESULTS: Ostarine Prophylaxis showed positive effects in preventing osteoporotic changes in cortical and trabecular bone (femoral trabecular density: 26.01 ± 9.1% vs. 20.75 ± 1.2% in Orx and in L4: 16.3 ± 7.3% vs 11.8 ± 2.9% in Orx); biomechanical parameters were not affected; prostate weight was increased (0.62 ± 0.13 g vs 0.18 ± 0.07 g in Orx). Ostarine Therapy increased solely the cortical density of the femur (1.25 ± 0.03 g/cm3 vs. 1.18 ± 0.04 g/cm3 in Orx); other bone parameters remained unaffected. Testosteron Prophylaxis positively influenced cortical density in femur (1.24 ± 0.05 g/cm3 vs. 1.18 ± 0.04 g/cm3 in Orx); Test. Therapy did not change any bony parameters. CONCLUSION: Ostarine Prophylaxis could be further investigated as a preventative treatment for male osteoporosis, but an androgenic effect on the prostate should be taken into consideration, and combination therapies with other anti-osteoporosis agents could be considered.

Predictive factors for docking site procedure in bone transport for large lower extremity segmental defects.

BACKGROUND: Segmental bone transport is a common technique for treating large segmental bone defects. However, a docking site procedure is often necessary in segmental bone transport. To date, no prognostic factors for the need of docking site procedure have been reported. Thus, the decision is often made at random, based on the surgeon's subjective judgment and experience. The aim of this study was to identify prognostic factors for the need of docking site operation. METHODS: Patients with segmental bone transport in lower extremity bone defects were included regardless of age, aetiology, and defect size. We excluded patients undergoing treatments that were not yet completed, and those who discontinued therapy by any reason. The need for docking site operation was modelled with logistical and linear regression as well as univariate analysis of variances (ANOVA). Receiver operating characteristics (ROC) curve analysis was also performed. RESULTS: Twenty-seven patients from age 12 to 74 years (mean age: 39.07 ± 18.20 years) were included. The mean defect size was 76.39 ± 41.10 mm. The duration of transport (days) showed a significant influence (p = 0.049, 95%CI: 1.00-1.02) on the need for docking site operation. No other significant influences were detected. CONCLUSION: A link between the duration of transport and the need for docking site operation was detected. Our data showed that if a threshold of about 188 days is exceeded, docking surgery should be considered.

[Interdisciplinary extremity board in the treatment of complex injuries]. / Interdisziplinäres Extremitäten-Board in der Behandlung von Komplexverletzungen.

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.

A combined treatment with selective androgen and estrogen receptor modulators prevents bone loss in orchiectomized rats.

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.

Combination of selective androgen and estrogen receptor modulators in orchiectomized rats.

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.

[3D printing in spinal surgery-Update]. / 3D-Druck in der Wirbelsäulenchirurgie ­ Update.

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 3­dimensional 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.

[Complication rate after femoral shaft fractures in childhood and adolescence depending on patient factors and treatment measures]. / Die Komplikationsrate nach Femurschaftfrakturen im Kindes- und Jugendalter in Abhängigkeit von Patientenfaktoren und Behandlungsmaßnahmen.

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 X­ray morphometric evaluation of data. The patient files and X­rays 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.

Effect of alendronate or 8-prenylnaringenin applied as a single therapy or in combination with vibration on muscle structure and bone healing in ovariectomized rats.

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.

[Posterior vertebral column resection for correction of kyphotic deformity due to osteoporotic fractures of the thoracic spine]. / Posterior vertebral column resection (PVCR) zur Korrektur von Hyperkyphosen bei osteoporotischen Frakturen der Brustwirbelsäule.

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.

[Pedicle subtraction osteotomy to correct rigid deformities]. / Pedikelsubtraktionsosteotomie zur Korrektur rigider Deformitäten.

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.

Evaluation of ostarine as a selective androgen receptor modulator in a rat model of postmenopausal osteoporosis.

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.

The Advantages of Bilateral Osteotomy Over Unilateral Osteotomy for Osteoporotic Bone Healing.

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.

Effect of zileuton on osteoporotic bone and its healing, expression of bone, and brain genes in rats.

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.

[Optimized resource mobilization and quality of treatment of severely injured patients through a structured trauma room alarm system]. / Optimierte Ressourcenmobilisation und Versorgungsqualität Schwerstverletzter durch eine strukturierte Schockraumalarmierung.

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 t­tests (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.

Effect of Strontium Ranelate on the Muscle and Vertebrae of Ovariectomized Rats.

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.

Effect of the lipoxygenase-inhibitors baicalein and zileuton on the vertebra in ovariectomized rats.

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.