Anatomically shaped locking plates for radial head and olecranon fracture fixation in Monteggia-like lesions.

BACKGROUND: Monteggia-like lesions are rare injuries. We retrospectively reviewed 40 consecutive patients with Monteggia-like lesions treated at a level I trauma center from 2009 to 2016. Clinical results were evaluated with a focus on the use of modern locking plates. OBJECTIVE AND METHODS: Twenty-eight patients had Bado type II fractures, 11 had Bado type I, and 1 had Bado type III. All patients were treated by plate fixation of the ulna with a locking compression plate or double mini-plates. Fixation or replacement was performed for radial head fractures. We characterized all fractures and recorded the range of motion (ROM); 100-point visual analog scale (VAS) scores for pain and function; Disabilities of the Arm, Shoulder and Hand (DASH) score; and Mayo Elbow Performance Score (MEPS). A follow-up rate of 78% was reached at an average of 36 months (range, 12-95 months). RESULTS: Stable fixation without recurrent instability was accomplished. The average ROM for flexion reached 130∘ with an extension deficit of 13∘. The sum of supination and pronation was 136∘. The VAS scores for pain and function were 20 and 75, respectively. The average MEPS and DASH scores were 84 and 28, respectively. Bado type I fractures had better outcomes for all variables, especially forearm rotation (p< 0.05). The complication rate was 22.5% and revision rate was 17.5%. CONCLUSION: This fracture repair technique can safely achieve good and excellent outcomes in most cases and is partly superior to previously published techniques. However, Bado type II fractures still have a risk of poor results.

Posttraumatic elbow agility and reduction of muscle force after intra-articular distal fractures of the humerus in adults.

BACKGROUND: Treatment of distal intra-articular humerus fractures is still a technical challenge. Until now, little is known about the regain of strength and elbow agility after surgical treatment of these fractures. Due to small collectives there is only limited data. OBJECTIVE: Investigation of regained strength and elbow agility in patients with intra-articular distal humerus fractures. METHODS: A total of 28 patients were treated with distal intra-articular humerus fractures followed up for an average period of 62.3 months. The following parameters were examined: Arthrosis, heterotopic ossification, functional outcome (MEPS, DASH score, LES) and isometric strength of the elbow in extension and flexion was tested in 30∘, 60∘ and 90∘ in a custom-made positioning device. RESULTS: There was a high complication rate with 32%. At the 60th month post injury, range of motion (ROM) of the elbow was 114∘ with a reduction of 32∘ compared to the contralateral uninjured side (p< 0.001). The highest reduction was seen in extension with an average loss of 16∘ (p< 0.001). Loss of motion correlated with the fracture severity regarding the AO-classification (r= 0.54, p< 0.01). The average regained muscle force was 81.5% in flexion and 92% in extension in comparison to the contralateral healthy side. Patients over 60 years had less range of motion and inferior results in the DASH score compared to younger patients. CONCLUSIONS: Functional impairment in terms of reduced ROM and muscle force is a common complication after distal intra-articular humerus fracture. Patients over 60 years have a higher deficit of motion in the injured elbow joint and an inferior clinical outcome. Superiority of modern angle-stable implants could yet not be shown.

Low vitamin D levels affect outcomes of orthopedic spinal surgery: An observational study in clinical practice.

BACKGROUND: Low vitamin D is a major risk factor for osteoporotic fractures. Evidence also suggests correlation between deficiency and musculoskeletal pain. OBJECTIVE: Non-interventional study in patients undergoing spine surgery to investigate links between vitamin D levels and clinical features. METHODS: 25-OH vitamin D levels were assessed in two cohorts: Cohort 1 (vertebral fractures; VF) and Cohort 2 (other spinal issues; excluding VF). Lab values as well as painDETECT questionnaires, VAS and Oswestry Disability Index (ODI) were recorded. Follow-up visits were conducted a few days and 6 weeks postoperatively. RESULTS: One hundred and nine patients were enrolled. Mean VAS measured 72 mm in Cohort 1 and 55 mm in Cohort 2. Mean vitamin D concentrations were 16.8 ± 11 ng/ml in Cohort 1 and 18.3 ± 11 ng/ml in Cohort 2. VAS and ODI significantly correlated with vitamin D levels. Median painDETECT scores were 9 in Cohort 1 and 16 in Cohort 2. Six weeks postoperatively mean VAS was 31.4 ± 28 mm in Cohort 1 and 23.3 ± 21 mm in Cohort 2. Median painDETECT scores were 5 in both cohorts. CONCLUSION: Interactions are apparent between neuropathic pain and vitamin D serum levels. Consequently, vitamin D should be monitored in all patients requiring spinal surgery.

Influence of radiofrequency kyphoplasty on pulmonary function.

BACKGROUND: Vertebral compression fractures (VCF) change the natural spinal alignment and inevitably lead to a decreased quality of life. OBJECTIVE: The aim of the study was to evaluate changes in pulmonary function after VCF were treated by radiofrequency kyphoplasty (RF-TVA). METHODS: Twenty-five patients were treated with RF-TVA and analyzed in 3 subgroups taking into account the spinal location of the VCF. Pain as measured by visual analogue scale (VAS), Oswestry-Disability-Index (ODI), vertebral height, forced expiratory volume in 1 second (FEV1), and peak expiratory flow (PEF) were assessed before, directly after and 30 days after RF-TVA. RESULTS: The mean vertebral height was improved in all subgroups, with a minor reduction from one to 30 days postoperatively. The mean VAS and ODI significantly decreased in the main and upper diaphragm groups from baseline to the follow-up after 30 days. Patients treated below the main diaphragm region showed a significant improvement of ODI and a clear trend to significant improvements of VAS. PEF and FEV1 were significantly improved in the main diaphragm group. FEV1 also increased significantly in the upper diaphragm group with a clear trend to significance in the lower diaphragm group. CONCLUSIONS: Results indicate that RF-TVA may improve pulmonary function especially in cases where fractures are located in the main spinal region of the diaphragm.

Interaction of radiation therapy and radiofrequency kyphoplasty in the treatment of myeloma patients.

BACKGROUND: 30% of myeloma patients suffer from vertebral compression fractures (VCF). Consequently, augmentation often becomes inevitable to prevent further problems. This study evaluated the interaction of radiation therapy (RT) and radiofrequency kyphoplasty (RFK) in the treatment of myeloma associated VCF. METHODS: Eighty-six myeloma patients with VCF were treated with RFK followed by radiation therapy (RFK group) or vice versa (RT group). Visual analgoue scale (VAS), Oswestry-Disability-Index (ODI), vertebral height and kyphosis angle were assessed preoperatively, 3-4 days, 3 and 6 months postoperatively. Adverse events like cement leakage or additional fractures were documented. RESULTS: Both groups achieved comparable outcomes, but the course of VAS and kyphosis angle differed. Early postoperative kyphosis angles improved significantly in the RFK group, but significantly worsened afterwards. The RT group showed a trend towards significantly improvement postoperatively and minor worsening afterwards. VAS remained constant in the RT group and worsened in the RFK group after 6 months. More cement leakages and additional fractures were noted in the RT group. CONCLUSIONS: RFK is an effective method for treating VCF in myeloma patients independent of treatment order with regard to radiation therapy. However, RT should be conducted after RFK to minimize risks of cement extrusion and additional fractures.

Two-year clinical results of patients with sacroiliac joint syndrome treated by arthrodesis using a triangular implant system.

BACKGROUND: Sacroiliac joint (SIJ) syndrome can cause various symptoms and may also be one reason for persistent low back pain, especially in patients with prior spinal fusions. If conservative treatments fail to improve symptoms, arthrodesis surgery can be considered. Minimally invasive approaches have emerged recently providing a good alternative to conventional methods. A novel triangular implant system (iFuse) can achieve an arthrodesis of the SIJ without the use of additional screws or bone material. OBJECTIVE: Aim of the present study was an evaluation of short-term safety and efficacy of the implant system. METHODS: Twenty-four patients were included in the study and treated with the iFuse system. In addition to demographic data, pain intensity (visual analogue scale) and functional impairment (Oswestry-disability index) were assessed prior to surgery and 1 month, 3 months, 6 months, 12 months and 24 months thereafter. During surgery and the follow up period all adverse events were documented and the correct implant position was controlled via plain radiographs. RESULTS: VAS scores and ODI improved significantly directly after surgery from 84.3 ± 9.2 mm to 40.7 ± 9.2 mm and from 76.8 ± 9.2% to 40.7 ± 9.2 % (p < 0.001). The ODI improved further to 31 ± 5.4% after 24 months whereas the VAS improved until the 3 months examination and ten stayed constant between 27.7 mm and 26.5 mm to 27 ± 6.6 mm at 24 months. No adverse events, intraoperative complications, implant malpositioning or loosening could be recorded at any time. CONCLUSIONS: The iFuse system is an effective and safe treatment for minimally invasive surgical arthrodesis of the SIJ. Pain and functional impairment can be significantly improved. However, in addition to this case series, further controlled studies are necessary, particularly in terms of a previous spinal fusion history.

Mid-term outcomes after radiofrequency-targeted vertebral augmentation in the treatment of myeloma associated vertebral fractures.

BACKGROUND: Myeloma patients often suffer from painful vertebral fractures (VCF) which impair their quality of life. Common methods for augmentation of the vertebrae are vertebroplasty, kyphoplasty and radiofrequency-targeted vertebral augmentation (RF-TVA). OBJECTIVE: This study evaluates the long-term effectiveness and safety of RF-TVA in the treatment of myeloma associated VCF. METHODS: Eighty-seven myeloma patients (mean age: 64.7 ± 9.5 years) with VCF were treated with RF-TVA. Patient data were assessed preoperatively and in five postoperative examinations up to 12 months. Pain was measured with the visual analogue scale (VAS) and the impairment was evaluated with the Oswestry-Disability-Index (ODI) at each examination. In addition, the mid vertebral height, kyphosis angle, and additional fractures were evaluated by x-rays. Furthermore, cement leakage was documented. RESULTS: The VAS values were significantly improved in comparison to the preoperative values (p≤ 0.001), but slightly fluctuating during the follow-up period. The ODI was also significantly improved (p≤ 0.001), but it showed a worsening from the 12 months evaluation to the 24 months evaluation. The kyphosis angle and the vertebral height were significantly improved after surgery (p = 0.03, p ≤ 0.001), but worsened steadily to the last follow up examination. Cement leakage was asymptomatic and occurred in 18% of the patients. In 10% of the patients additional fractures were detected in the 24 months evaluation. CONCLUSIONS: The results of our study show that RF-TVA is a safe treatment for myeloma associated vertebral compression fractures, which achieves an acceptable improvement of patient's pain and quality of life.

Temperature distribution during radiofrequency ablation of spinal metastases in a human cadaver model: Comparison of three electrodes.

BACKGROUND: Radiofrequency ablation (RFA) temperatures reaching 45°C in adjacent tissues are cytotoxic to the spinal cord, nerves and surrounding tissues. OBJECTIVE: This study compares different RFA electrodes with regard to the temperature distribution during ablation of spinal metastases. METHODS: In vitro experimental study in isolated lumbar vertebrae of a human cadaveric spine. The temperature distribution of RFA electrodes was measured during ablation in human cadaveric lumbar vertebrae containing a simulated vertebral body lesion. The analysis compared a novel bipolar RFA electrode with two conventional monopolar RFA electrodes. A vertebral metastasis model was prepared in eight lumbar vertebrae for each electrode. Differences between the electrodes were evaluated with a one-way ANOVA. RESULTS: The lowest temperature at the thermocouples adjacent to the simulated lesion was achieved when using the bipolar RFA electrode (46.4 ± 3.3°C), but temperature difference to the monopolar RFA electrodes was not significant. In the neural foramen and epidural space of lumbar vertebrae the maximal temperature measured when using the bipolar RFA electrode was 37.0 ± 0°C and 37.3 ± 0.7°C, which was significantly lower than during ablation via either of the monopolar RFA electrodes (p ≤ 0.001). CONCLUSIONS: Temperatures in areas of adjacent tissue during RFA using a specific for spinal ablation designed electrode with integrated thermocouples were significantly lower compared to other electrodes, potentially reducing temperature related risks during ablation.

Clinical efficacy and safety of a new flexible interbody spacer system.

BACKGROUND: Patients with lumbar degenerative disk disease (DDD) often require an interbody fusion. Several spacer systems have been developed to achieve an adequate fusion. The newly developed flexible interbody spacer system (Luna®, Benvenue Medical Inc.) expands to the disk space and is adjustable to the patient's anatomy. OBJECTIVE: Prospective monocentric evaluation of interbody fusions performed with the new system in patients with DDD to assess the device's efficacy and safety. METHODS: The study includes patients with DDD of one or two contiguous lumbar levels. All patients were treated with the new flexible cage system. To evaluate the clinical outcome, examinations were conducted preoperatively, 6 weeks, 6 months and 12 months postoperatively. At each study visit possible implant loosening was assessed by plain radiography and any adverse events were documented. Furthermore, back pain was evaluated using the visual analogue scale (VAS), functional impairment using the Oswestry-Disability-Index (ODI) and quality of life using the SF36. RESULTS: A total of 30 patients (age: 52.8 ± 11 years, gender: 53% male) were included. None of the patients showed signs of implant loosening and the total number of adverse events was low (3%). The VAS improved significantly from 81.2 ± 9.5 mm at baseline to 28 ± 26.2 mm after 12-months (p ≤ 0.0001). The ODI also improved significantly from 57.9 ± 9.6% at baseline to 20 ± 15.6% after 12-months (p ≤ 0.0001). The physical component score (PCS) of the SF36 improved significantly ongoing from 29.2 ± 9.3 at baseline to 56.1 ± 14.9 after 12-months (p = 0.0079) and the mental component score (MCS) improved significantly from 49.2 ± 20.7 at baseline to 62.8 ± 18.9 after 12 months (p = 0.013). CONCLUSIONS: Minimal-invasive lumbar interbody fusion with the new flexible system is a safe and effective treatment method for patients with DDD. Complication rates are low and treatment leads to an improvement of pain, functional impairment and quality of life.

Influence of smoking on spinal fusion after spondylodesis surgery: A comparative clinical study.

BACKGROUND: Smoking is a risk factor in the process of bone healing after lumbar spondylodesis, often associated with complications that occur intraoperatively or during follow-up periods. OBJECTIVE: To assess if smokers yield worse results concerning lumbar interbody fusion than non-smokers in a clinical comparative setting. METHODS: Spondylodesis outcomes in 50 patients, 34 non-smokers (mean 58 years; (range 29-81) and 16 smokers (mean 47 years; range 29-75) were compared preoperatively and one year after spondylodesis surgery using Oswestry-Disability-Index (ODI), visual analogue scale (VAS) and radiological outcome analysis of fusion-success. RESULTS: Smokers showed a comparable ODI-improvement (p = 0.9343) and pain reduction to non-smokers (p = 0.5451). The intake of opioids was only reduced in non-smokers one year after surgery. Fusion success was significantly better in non-smokers (p = 0.01). CONCLUSIONS: The results indicate that smoking adversely effects spinal fusion. Particularly re-operations caused by pseudarthrosis occur at a higher rate in smokers than in non-smokers.

Medium-term results after complex intra-articular fractures of the tibial plateau.

BACKGROUND: To present the medium-term results of intra-articular, bicondylar AO/OTA classification type C fractures of the tibial plateau in a retrospective study at a level-1 trauma center in 22 patients with 23 fractures. METHODS: Demographic data for the patients and details of current clinical and radiological follow-up findings were obtained to assess range of motion, clinical stability and alignment of the knee, and posttraumatic arthrosis (Kellgren/Lawrence score). Functional outcomes were assessed using the Lysholm score, Knee Injury and Osteoarthritis Outcome Score (KOOS), and International Knee Documentation Committee (IKDC) form. RESULTS: Patients' mean age was 46 years (range 20-67 years). Leading causes of the fractures were high-energy traffic accidents and falls. There were seven C1, seven C2, and nine C3 fractures. ORIF was performed in 20 patients; in two patients an external fixator and in one patient cannulated screws alone were used. In 13/22 patients, an angle-stable locking plate (Less Invasive Stabilization System, LISS) was used for osteosynthesis. The mean follow-up period was 67 months (range 36-109 months). The overall complication rate was 39.1%, including four infections and four cases of pseudarthrosis (17.4%). The average flexion of the injured knee was significantly lower in comparison with the contralateral side (124.9° vs. 135.2°). Knee stability did not differ statistically significantly. Current radiographs revealed no signs of posttraumatic arthrosis in 30.4% of cases, mild signs in 34.8%, clear signs in 26.1%, and severe signs in 13% using the Kellgren and Lawrence scale. The average Lysholm score was 66.2 points, and the average KOOS score was 67.84. One patient was in category A, and 2 were in category B in the IKDC overall categories, whereas 5 patients were in category C and 14 were even in category D. CONCLUSIONS: Complex articular tibial plateau fractures are associated with a high rate of complications, continue to have a severe impact on function in the injured knee, lead to early post-traumatic arthrosis, and result in long-lasting subjective symptoms for the patients.

Subtrochanteric femoral fractures: influence of patient age on fracture type and mobility.

BACKGROUND: To investigate the potential influence of patient age on fracture type and postoperative mobility in subtrochanteric femoral fractures. METHODS: Data for patients who had suffered subtrochanteric femoral fractures between 2004 and 2009 were analyzed in a retrospective single-center study at a level I trauma center. Age, sex, accident cause, fracture type (Seinsheimer, Russell-Taylor, and AO classifications) and mobility at different time points (pre-trauma, after 3, 6, and 12 months, and current) were collected using the patient files, radiographs, and phone enquiries. The patients were divided into groups aged <65 and ≥65 years. Significant associations between age and fracture type and mobility were investigated using Fisher's exact test, Levene's test, t test, and Mann-Whitney U test. RESULTS: A total of 91 patients were evaluated. There were 38 patients in group I (<65 years) and 53 in group II (≥65 years). The trauma leading to the fracture was greater in group I than in group II (P < 0.01), and group I also had a larger number of concomitant injuries (P < 0.01). There was a smaller proportion of women in group I (38 vs. 75.5 %; P < 0.01). Group II had higher grades in the Russell-Taylor fracture classification (P < 0.05) and more frequently had type A fractures in the AO classification (P < 0.05). No differences between the groups were found when the Seinsheimer classification was applied. With regard to postoperative mobility, there was better mobility in group I after 12 months and at the last follow-up examination (P < 0.01). CONCLUSIONS: Older patients (≥65 years old) more often had type II fractures according to the Russell-Taylor classification, type A fractures in the AO classification, and poorer postoperative mobility over the long term than patients <65 years old.

Results of dynamic pedobarography following surgically treated intra-articular calcaneal fractures.

OBJECTIVE: To investigate the clinical outcome and gait analysis findings by dynamic pedobarography in patients following surgically treated single, closed, dislocated intra-articular calcaneal fractures. DESIGN: Retrospective single-center study with 26 patients. The average follow-up period was 34 months (range 18-61 months). We used the Zwipp score and a score based on a visual analog scale (VAS) to assess the subjective and objective clinical outcome. Dynamic pedobarography (EMED-M, 38 × 42 cm, four sensors per square centimeter, 50 Hz; Novel GmbH., Munich, Germany) was performed to retrieve gait patterns. Analysis was performed using the Emed-Software (Novel GmbH., Munich, Germany). RESULTS: For the Zwipp score (±200 points), the average was +54.4 points (±48.2); for the VAS score (0-100 points), the average was 58.3 points (±24.3). There was limited mobility in the upper and lower ankle joint. Pedobarography showed a clearly disturbed gait with increased pressure for the fractured side (157 vs. 119 kPa) in the midfoot region (71.8 vs. 68 kPa) and under fifth metatarsal bone (234 vs. 160 kPa). The gait line was lateralized. The force-time-integral (fractured vs. healthy side) showed significant differences for the medial (18 vs. 7 N s) and lateral (61 vs. 36 N s) midfoot region. CONCLUSIONS: We found only an average clinical outcome and clear pathological gait patterns in our cohort with lateralization of the gait line.

The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors.

Primary osteoporosis is an age-related disease characterized by an imbalance in bone homeostasis. While the resorptive aspect of the disease has been studied intensely, less is known about the anabolic part of the syndrome or presumptive deficiencies in bone regeneration. Multipotent mesenchymal stem cells (MSC) are the primary source of osteogenic regeneration. In the present study we aimed to unravel whether MSC biology is directly involved in the pathophysiology of the disease and therefore performed microarray analyses of hMSC of elderly patients (79-94 years old) suffering from osteoporosis (hMSC-OP). In comparison to age-matched controls we detected profound changes in the transcriptome in hMSC-OP, e.g. enhanced mRNA expression of known osteoporosis-associated genes (LRP5, RUNX2, COL1A1) and of genes involved in osteoclastogenesis (CSF1, PTH1R), but most notably of genes coding for inhibitors of WNT and BMP signaling, such as Sclerostin and MAB21L2. These candidate genes indicate intrinsic deficiencies in self-renewal and differentiation potential in osteoporotic stem cells. We also compared both hMSC-OP and non-osteoporotic hMSC-old of elderly donors to hMSC of ∼30 years younger donors and found that the transcriptional changes acquired between the sixth and the ninth decade of life differed widely between osteoporotic and non-osteoporotic stem cells. In addition, we compared the osteoporotic transcriptome to long term-cultivated, senescent hMSC and detected some signs for pre-senescence in hMSC-OP.Our results suggest that in primary osteoporosis the transcriptomes of hMSC populations show distinct signatures and little overlap with non-osteoporotic aging, although we detected some hints for senescence-associated changes. While there are remarkable inter-individual variations as expected for polygenetic diseases, we could identify many susceptibility genes for osteoporosis known from genetic studies. We also found new candidates, e.g. MAB21L2, a novel repressor of BMP-induced transcription. Such transcriptional changes may reflect epigenetic changes, which are part of a specific osteoporosis-associated aging process.

Biomechanical comparison of the Locking Compression superior anterior clavicle plate with seven and ten hole reconstruction plates in midshaft clavicle fracture stabilisation.

PURPOSE: The purpose of this study was to characterise the biomechanical properties of the seven hole superior anterior clavicle LCP (locking compression plate) and to compare these with the properties of commonly applied implants used for the stabilisation of clavicular midshaft fractures such as the locking 7- and ten hole reconstruction plate. METHODS: Twenty-four synthetic clavicles were used. A transverse midshaft fracture was induced. The clavicles were fixed with angle stable clavicle LCPs, seven hole and ten hole reconstruction plates (n = 8 each). Twenty cycles of axial compression and torsion were performed for each sample, which was followed by 1,000 cycles of three point bending and ultimately bending to failure. Axial, torsional and cantilever bending stiffness were calculated from the data recorded. RESULTS: The clavicle LCP showed the highest overall stiffness compared to the seven and ten hole reconstruction plate. Significantly higher stiffness values were found for axial compression and external rotation. In the load-to-failure tests, the ten hole reconstruction plate especially showed early signs of plastic deformation, which might account for early plate insufficiency so frequently observed clinically. CONCLUSION: The results indicate that the clavicle LCP, as compared to the reconstruction plates, leads to superior biomechanical stability in the treatment of midshaft clavicle fractures.

Simultaneous posterior fracture dislocation of the shoulder following epileptic convulsion.

Shoulder dislocations with fractures are a possible complication of an epileptic seizure and are often missed on the first sight. The incidence of sustaining an avascular humeral head necrosis (AVN) is high, and primary prosthetic replacement is the choice of treatment. In this paper, we describe such a rare case: a 48-year-old male patient sustained simultaneous bilateral posterior shoulder dislocation with fractures of both humeral heads following the first episode of an epileptic convulsion. On the left side, open reduction and internal fixation were performed with angle stable plate osteosynthesis. In the same operation, a hemi-prosthesis was implanted on the right side. One and a half years postoperatively, function on the right side is unsatisfying and AVN is seen on the left side and secondary prosthetic replacement had to be performed. In case of a shoulder dislocation with a complex fracture after an epileptic seizure, prosthetic replacement is the choice of treatment.

Effects of low-energy NMR on posttraumatic osteoarthritis: observations in a rabbit model.

OBJECTIVE: To evaluate a possible beneficial effect of low-energy nuclear magnetic resonance (NMR) on cartilage in moderate and severe posttraumatic osteoarthrosis in the rabbit using a macroscopic and a histological grading system. DESIGN: Following transection of the anterior cruciate ligament of both knees in 24 skeletally mature New Zealand White rabbits, we observed different stages of osteoarthrosis (OA) 6 and 12 weeks postoperatively. Animals were randomized into four groups: Group 1 (eight animals) was treated after 6 weeks by NMR (magnetic field: 20-40 G, interference field: 2.35 mT, 100 kHz; MBST Device, MedTec, Germany), with 1 h of treatment for seven consecutive days. Group 2 was treated in the same pattern after 12 weeks. The sham-operated groups 3 and 4 received no treatment. Seven days after the last treatment, OA was macroscopically graded and hyaline cartilage of the load bearing area was evaluated histologically according to the Mankin scale. RESULTS: Macroscopically, there was less OA in group 1 (p < 0.01), but did not reveal significance in group 2 (p = 0.11) compared to the sham groups. There was no significant difference in the Mankin score in both of the treated groups compared to the control groups (group 1: p = 0.36; group 2: p = 0.81). CONCLUSIONS: The results showed some beneficial macroscopic effect in mild OA with less macroscopic OA signs in the treated animals but without a histological effect in the Mankin scale. There was no effect found in the pattern later OA. On behalf of these results, NMR for the treatment of posttraumatic OA cannot be recommended at this point of time.

Functional and proteomic analysis of serum and cerebrospinal fluid derived from patients with traumatic brain injury: a pilot study.

BACKGROUND: An enhanced fracture healing response has been reported in patients with traumatic brain injury (TBI). This has been attributed to circulating humoral factors that are thought to be proteins produced and released by the injured brain. However, these factors remain unknown. The aim of this study was to identify osteogenic factors in serum and cerebrospinal fluid (CSF) from TBI patients. This was carried out using in vitro proliferation assays with the human foetal osteoblastic 1.19 cell line (hFOB) combined with a novel proteomic approach. METHODS: Serum was collected from brain-injured (n = 12) and non-brain-injured (n = 9) patients with a comorbid femur shaft fracture. Similarly, CSF was obtained from TBI (n = 7) and non-TBI (n = 9) patients. The osteoinductive potential of these samples was determined by measuring the in vitro proliferation rate of hFOB cells. Highly osteogenic serum and CSF samples of TBI patients were chosen for protein analysis and were compared to those of non-brain-injured patients. A new hFOB cell-based method was used to enrich the proteins in these samples, which had a functional affinity for these osteoprogenitor cells. These enriched protein fractions were mapped using two-dimensional gel electrophoresis and protein imaging methods displaying serum and CSF proteins of brain-injured and control subjects that had an affinity for human osteoprogenitor cells. RESULTS: Serum and CSF derived from brain-injured patients demonstrated a greater osteoinductive potential (P < 0.05) than their non-brain-injured counterparts. Clear-cut differences in the pattern of proteins in two-dimensional gels were detected between TBI and control patients. Fourteen proteins were exclusively present in the serum of TBI patients, while other proteins were either up- or downregulated in samples collected from TBI patients (P < 0.05). CONCLUSION: Osteoinductive factors are present in the serum and CSF of brain-injured patients. These may include one or more of those proteins identified as having an affinity for osteoprogenitor cells that are either exclusively present or up- or downregulated in the serum and CSF of brain-injured patients.

Serum after traumatic brain injury increases proliferation and supports expression of osteoblast markers in muscle cells.

BACKGROUND: Traumatic brain injury is associated with an increased rate of heterotopic ossification within skeletal muscle, possibly as a result of humoral factors. In this study, we investigated whether cells from skeletal muscle adopt an osteoblastic phenotype in response to serum from patients with traumatic brain injury. METHODS: Serum was collected from thirteen patients with severe traumatic brain injury, fourteen patients with a long-bone fracture, and ten control subjects. Primary cultures of skeletal muscle cells isolated from patients undergoing orthopaedic surgery were performed and characterized with use of immunofluorescence microscopy, reverse transcription-polymerase chain reaction, and Western blot analysis. Proliferation and osteoblastic differentiation were assessed with use of commercial cell assays, Western blot analysis (for Osterix protein), and the Villanueva bone stain. RESULTS: All serum-treated cell populations expressed the osteoblast marker Osterix after one week in culture. Cells treated with serum from all study groups in mineralization medium had increased alkaline phosphatase activity and mineralized nodules within the mesenchymal cell subpopulation after three weeks in culture. Serum from patients with traumatic brain injury induced a significant increase (p = 0.02) in the rate of proliferation of primary skeletal muscle cells (1.87 [95% confidence interval, 1.66 to 2.09]) compared with the rate induced by serum from patients with a fracture (1.42 [95% confidence interval, 1.21 to 1.58]) or by serum from controls (1.35 [95% confidence interval, 1.15 to 1.54]). CONCLUSIONS: Human serum supports the osteoblastic differentiation of cells derived from human skeletal muscle, and serum from patients with severe traumatic brain injury accelerates proliferation of these cells. These findings suggest the early presence of humoral factors following traumatic brain injury that stimulate the expansion of mesenchymal cells and osteoprogenitors within skeletal muscle.

Serum-mediated osteogenic effect in traumatic brain-injured patients.

BACKGROUND: Patients with a traumatic brain injury (TBI) and bone fractures often show an enhanced fracture healing, as well as an increased incidence of heterotopic ossifications (HO). It has been suggested that unknown osteoinductive factors may be released by the injured brain into the systemic blood circulation and act peripherally on the affected tissues. The aim of this study was to investigate whether serum from TBI patients is osteoinductive. METHODS: Sixty-one consecutive patients were classified into four groups: TBI and long-bone fracture (group I, n = 12), isolated severe TBI (group II, n = 21), isolated long-bone fracture (group III, n = 19) and controls (group IV, n = 9). Blood samples were collected at 6, 24, 72 and 168 h post-injury. The osteogenic potential was determined by measuring the in vitro proliferation rate of the human fetal osteoblastic cell line hFOB1.19, and primary human osteoblasts. Additionally, serum induced osteoblastic differentiation was assessed by measuring the mRNA expression of specific osteoblastic markers, including alkaline phosphatase, runt-related transcription factor 2, cathepsin K and serine protease 7. RESULTS: The sera of group I induced a higher mean proliferation rate of primary human osteoblasts at all time points of sampling than group III (P < 0.05). Group I had a higher mean proliferation rate of hFOB1.19 cells than all other groups at 6, 24 and 72 h post-injury (P < 0.05). The expression of alkaline phosphatase, cathepsin K and runt-related transcription factor 2 mRNA was increased in group I compared with group III and serine protease 7 was exclusively expressed in group I. CONCLUSION: The study results strongly support a humoral mechanism in enhanced fracture healing and the induction of HO after TBI. Increased proliferation of osteoblastic cells and an accelerated differentiation of osteoprogenitor cells may be responsible for increased osteogenesis in TBI.