Close negative correlation of local and circulating Dickkopf-1 and Sclerostin levels during human fracture healing.

Wnt signaling is critically involved in fracture healing. Existing data predominantly relies on rodent models. Here, we explored local and circulating Dickkopf-1 (DKK1) levels in patients with respect to fracture healing and explore its association to sclerostin (SOST). 69 patients after surgical stabilization of long bone fractures of which six patients had impaired fracture healing were included in this study. Life-style and patient related factors with a known effect on DKK1 and SOST were recorded. DKK1 and SOST concentrations were measured using enzyme-linked immunosorbent assay (ELISA) at the fracture site and in circulation. DKK1 and SOST showed a close inverse correlation. In fracture hematoma and immediately after trauma DKK1 levels were significantly reduced while SOST levels were significantly increased, compared to healthy control. Postoperatively, DKK1 peaked at week 2 and SOST at week 8, again demonstrating a close negative correlation. Age and smoking status affected the balance of DKK1 and SOST, while type 2 diabetes and sex did not demonstrate a significant influence. Early postoperative elevation of SOST without compensatory DKK1 decrease was associated with fracture non-union in younger patients (< 50a). The close inverse correlation and very rapid dynamics of DKK1 and SOST locally as well as systemically suggest their critical involvement during human fracture healing. Importantly, as immediate compensatory feedback mechanism are apparent, we provide evidence that dual-blockade of DKK1 and SOST could be critical to allow for therapeutic efficiency of Wnt targeted therapies for fracture healing.

Does surgical reconstruction of the distal oblique bundle (DOB) provide similar stability as the intact bundle or Adams procedure? A systematic review.

INTRODUCTION: The aim of this review was to summarize the available evidence for biomechanical stability following surgical DOB reconstruction, and to determine whether distal radioulnar joint (DRUJ) stability with a reconstructed DOB was similar to the native intact condition or that after the Adams procedure. MATERIAL AND METHODS: A systematic literature search according to the PRISMA guidelines was performed using the databases PubMed and Embase. The following search algorithm was used: ("DOB" OR "Distal Oblique Bundle") AND "Reconstruction". Biomechanical or human cadaveric studies that measured stability of the DRUJ after reconstruction of the DOB were included. RESULTS: Four articles were included in the final analysis. DOB incidence was reported to be between 50% and 70%. Two studies observed no differences between the intact situation and the reconstructed DOB, respectively the Adams procedure. A further author group found no signs of major instability after the Adams reconstruction or after DOB reconstruction, except for decreased stability during supination in the DOB sample. In another study, similar results could be shown for the Adams and DOB reconstruction groups; however, the DOB sample showed decreased dorsal translation of the radius during forearm supination. CONCLUSION: In conclusion, DOB reconstruction was proven to stabilize the DRUJ adequately. Moreover, the reconstructed DOB showed the same stability as the native DOB, except for one study, in which stability following reconstruction was reduced during supination. No significant difference between the DOB and the Adams reconstruction could be observed.

Radiographic Outcomes of Conservative and Operative Treatment in Isolated L1 Fractures.

Background and Objectives: The adequate therapy of thoracolumbar fractures in the elderly population is still controversially discussed. The aim of this study was to evaluate and compare the results of conservatively and surgically treated younger (≤60a) and elderly patients (>60a) with fractures of L1. Materials and Methods: Patients (231) with isolated L1 fractures were included and treated at the University Clinic of Orthopedics and Trauma Surgery, Division of Trauma Surgery, Medical University of Vienna, during the observation period of 2012-2018. Results: Conservative treatment led to a significant increase in the vertebral and bi-segmental kyphosis angle in both age groups (young vertebral: p = 0.007; young bi-segmental: p = 0.044; old vertebral: p = 0.0001; old bis-segmental: p = 0.0001). A significant reduction in the vertebral angle in both age groups was achieved after operative treatment (young: p = 0.003, old: p = 0.007). The bi-segmental angle did not significantly improve after surgery in both age groups (≤60a: p = 0.07; >60a: p = 1.0). Conclusions: The study shows that conservative treatment does not seem to be sufficient for a correction of radiological parameters in young and elderly patients. In contrast, operative treatment led to a significant improvement of the vertebral kyphosis angle, without changing the bi-segmental kyphosis angle. These results suggest a greater benefit from operative treatment in patients ≤ 60a than in older patients.

The influence of M-CSF on fracture healing in a mouse model.

Macrophage colony-stimulating factor 1 (M-CSF) is known to play a critical role during fracture repair e.g. by recruiting stem cells to the fracture site and impacting hard callus formation by stimulating osteoclastogenesis. The aim of this experiment was to study the impact of systemic M-CSF application and its effect on bony healing in a mouse model of femoral osteotomy. Doing so, we studied 61 wild type (wt) mice (18-week-old female C57BL/6) which were divided into three groups: (1) femoral osteotomy, (2) femoral osteotomy + stabilization with external fixator and (3) femoral osteotomy + stabilization with external fixator + systemic M-CSF application. Further, 12 op/op mice underwent femoral osteotomy and served as proof of concept. After being sacrificed at 28 days bony bridging was evaluated ex vivo with µCT, histological and biomechanical testing. Systemic M-CSF application impacted osteoclasts numbers, which were almost as low as found in op/op mice. Regarding callus size, the application of M-CSF in wt mice resulted in significantly larger calluses compared to wt mice without systemic M-CSF treatment. We further observed an anabolic effect of M-CSF application resulting in increased trabecular thickness compared to wt animals without additional M-CSF application. Systemic M-CSF application did not alter biomechanical properties in WT mice. The impact of M-CSF application in a mouse model of femoral osteotomy was oppositional to what we were expecting. While M-CSF application had a distinct anabolic effect on callus size as well as trabecular thickness, this on bottom line did not improve biomechanical properties. We hypothesize that in addition to the well-recognized negative effects of M-CSF on osteoclast numbers this seems to further downstream cause a lack of feedback on osteoblasts. Ultimately, continuous M-CSF application in the absence of co-stimulatory signals (e.g. RANKL) might overstimulate the hematopoietic linage in favor of tissue macrophages instead of osteoclasts.

Different storage times and their effect on the bending load to failure testing of murine bone tissue.

Cryopreservation is a well-established method for bone storage. However, the ideal timing of mechanical testing after sacrificing the experimental animals is still under discussion and of significant importance to the presentation of accurate results. Therefore, the aim of this study was to investigate and compare different cryopreservation durations to native murine bone and whether there was an influence on mechanical bone testing. For this study the tibias of 57 female C57BL/6 mice-18-weeks of age-were harvested and randomly allocated to one of four groups with varying storage times: (1) frozen at -80 °C for 3 months, (2) frozen at -80 °C for 6 months, (3) frozen at -80 °C for 12 months and (4) native group. The native group was immediately tested after harvesting. The comparison of the mean strength and load to failure rates demonstrated a significant difference between the storage groups compared to the native control (p = 0.007). However, there was no difference in the strength and the load to failure values of bones of all storage groups when compared against each other. Once cryopreservation at -80 °C is performed, no differences of mechanical bone properties are seen up to 12 months of storage. When actual in vivo data is of close interest, immediate testing should be considered and is preferred. If comparison of groups is required and long-time storage is necessary, cryopreservation seems to be an accurate method at present.

Author Correction: Effect of two (short-term) storage methods on load to failure testing of murine bone tissue.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Circulating Myostatin Levels Decrease Transiently after Implantation of a Hip Hemi-Arthroplasty.

INTRODUCTION: Muscle and bone metabolism are both important for the healing of fractures and the regeneration of injured muscle tissue. The aim of this investigation was to evaluate myostatin and other regulating factors in patients with hip fractures who underwent hemi-arthroplasty. METHODS: Serum levels of myostatin (MSTN), follistatin (FSTN), dickkopf-1 (Dkk1), and periostin (PSTN) as well as markers of bone turnover were evaluated in patients with hip fractures before surgery and twice in the 2 weeks after surgery. These parameters were also evaluated in age- and gender-matched subjects without major musculoskeletal injury. RESULTS: MSTN was transiently reduced; its opponent FSTN was transiently increased. Dkk1, the negative regulator of bone mass, and PSTN, a marker of subperiosteal bone formation, increased after surgery. With regard to markers of bone turnover, resorption was elevated during the entire period of observation whereas the early bone formation marker N-terminal propeptide of type I collagen was elevated 12 days after surgery. CONCLUSIONS: Unexpectedly, MSTN, a negative regulator of muscle growth, was reduced after surgery compared with before surgery. As musculoskeletal markers are altered during bone healing, they do not reflect general bone metabolism after fracture or joint arthroplasty. This is important because many elderly patients receive treatment for osteoporosis.

Bisegmental posterior stabilisation of thoracolumbar fractures with polyaxial pedicle screws: Does additional balloon kyphoplasty retain vertebral height?

We retrospectively evaluated single-level compression fractures (T12-L3) scheduled for a short-segment POS (posterior-only stabilization) using polyaxial screws. Patients averaged 55.7 years (range, 19-65). Patients received either POS or, concomitantly, BK (balloon kyphoplasty) of the fractured vertebrae as well. Primary endpoint was the radiological outcome at the last radiographic follow-up prior to implant removal. POS together with BK of the fractured vertebrae resulted in a significant improvement of the local kyphosis angle and vertebral body compression rates immediately post-OP. During the further course of FU, a considerable loss of correction was observed post-OP in both groups. (Local KA: pre-OP/ post-OP/ FU: 12.6±4.8/ 3.35±4.8/ 11.6±6.0; anterior vertebral body compression%: pre-OP/post-OP/ FU: 71.94±12.3/ 94.78±19.95/ 78.17±14.74). VAS was significantly improved from 7.2±1.3 pre-OP to 2.7±1.3 (P<0.001) at FU. We found a significant restoration of the vertebral body height by BK. Nevertheless, follow-up revealed a noticeable loss of reduction. Given the fact that BK used together with polyaxial screws did not maintain intra-operative reduction, our data do not support this additional maneuver when used together with bi-segmental polyaxial pedicle screw fixation.

Survival rate and Outcome of extracorporeal life support (ECLS) for treatment of acute cardiorespiratory failure in trauma patients.

Extracorporeal life support (ECLS) remains the last option for cardiorespiratory stabilization of severe traumatic injured patients. Currently limited data are available and therefore, the current study assessed the survival rate and outcome of ECLS in a Level I trauma center. Between 2002 and 2016, 18 patients (7 females, 11 males) with an median age of 29.5 IQR 23.5 (range 1-64) years were treated with ECLS due to acute traumatic cardiorespiratory failure. Trauma mechanism, survival rate, ISS, SOFA, GCS, GOS, CPC, time to ECLS, hospital- and ICU stay, surgical interventions, complications and infections were retrospectively assessed. Veno-arterial ECLS was applied in 15 cases (83.3%) and veno-venous ECLS in 3 cases (16.6%). Survivors were significant younger than non-survivors (p = 0.0289) and had a lower ISS (23.5 (IQR 22.75) vs 38.5 (IQR 16.5), p = n.s.). The median time to ECLS cannulation was 2 (IQR 0,25) hours in survivors 2 (IQR 4) in non-survivors. Average GCS was 3 (IQR 9.25) at admission. Six patients (33.3%) survived and had a satisfying neurological outcome with a mean GOS of 5 (IQR 0.25) (p = n.s.). ECLS is a valuable treatment in severe injured patients with traumatic cardiorespiratory failure and improves survival with good neurological outcome. Younger patients and patients with a lower ISS are associated with a higher survival rate. Consideration of earlier cannulation in traumatic cardiorespiratory failure might be beneficial to improve survival.

The impact of nonosteogenic factors on the expression of osteoprotegerin and RANKL during human fracture healing.

OBJECTIVES: The osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) balance is of the utmost importance in fracture healing. The aim of this study was therefore to investigate the impact of nonosteogenic factors on OPG and RANKL levels. METHODS: Serum obtained from 51 patients with long bone fractures was collected over 48 weeks. The OPG and serum sRANKL (soluble RANKL) concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Smoking habit, diabetes, and alcohol consumption were recorded. RESULTS: Age and sex greatly influenced preoperative serum levels of OPG and sRANKL but differences were even more pronounced during fracture healing. Statistical significance was observed for overall serum levels of OPG (p = 0.001) and sRANKL (p < 0.001) in older men and women (age greater than 50 years). Interestingly, OPG levels increased over time in older women but decreased over time in older men. CONCLUSION: These data suggest that nonosteogenic factors, most significantly age and sex, have a major impact on sRANKL and OPG levels. Given the established association of OPG and sRANKL levels and nonunion, these findings seem to be of clinical relevance.Cite this article: J. Starlinger, G. Kaiser, A. Thomas, K. Sarahrudi. The impact of nonosteogenic factors on the expression of osteoprotegerin and RANKL during human fracture healing. Bone Joint Res 2019;8:349-356. DOI: 10.1302/2046-3758.87.BJR-2018-0116.R3.

Effect of two (short-term) storage methods on load to failure testing of murine bone tissue.

Since mechanical testing of bone quality is often delayed following euthanasia, the method of bone storage is of high importance in animal studies. Different storage methods may cause a change in the properties of bone tissue during mechanical testing. Therefore, the aim of this study was to investigate the biomechanical effects of two different fixation methods for bone tissue. We hypothesized that there is a difference between the load to failure values between the two groups. The tibias of fifteen 18-week-old female C57BL/6 mice were harvested and randomly allocated to three different groups with varying storage methods: (1) frozen at -80 °C, (2) paraformaldehyde working solution, and (3) native group. A storage time of two weeks prior to testing was chosen for groups 1 and 2. In group 3, referred to as the "native group", bones were immediately tested after the harvesting procedure. The comparison of the mean load to failure of all 3 groups (group 1: 28.7 N ± 6.1 N, group 2: 23.8 N ± 3.8 N and group 3: 23.7 N ± 5.7 N) did not reveal a significant difference. There was also no difference in strength or stiffness. The findings of the present study demonstrate that the two most common storage methods, do not have an influence on the biomechanical properties of murine bone over a two week period.

Distal tibial fractures: evaluation of different fixation techniques.

PURPOSE: The purpose of this study was the comparison of the most commonly used surgical techniques (external fixation, intramedullary nailing, and plate fixation) for the treatment of distal tibial fractures (AO/OTA classification 42-A, B, C or 43-A, B1). METHODS: A retrospective cohort study of patients who underwent surgical treatment for distal tibial fractures between 1992 and 2011 was performed. RESULTS: A total of 93 patients (52 male/41 female) met inclusion criteria. Statistically significant differences were found regarding the consolidation time of the intramedullary-nailing (147.32 ± 91.16 days) and the plate-fixation group (135.75 ± 110.75 days) versus the external-fixation group (163.12 ± 96.79 days; P = 0.001; P = 0.01). Significant differences were also observed in the range of motion (ROM) of the ankle joint in the intramedullary-nailing and plate-fixation group versus the ROM in the external-fixation group (P = 0.044; P = 0.025). The overall complication rate was 13/93 (14 %). Out of 66 patients treated with intramedullary nailing, 8 (12 %) suffered from complications. Out of the 15 patients treated with plate and 12 patients with external fixation, 2 (13 %) and 3 (25 %) showed complications, respectively. CONCLUSION: Our results demonstrate advantages in terms of shorter mobilization time and a better ROM of the ankle joint for intramedullary nailing and plate fixation compared with external fixation. Due to our results, we suggest internal fixation (intramedullary nailing or plate fixation) whenever patient's condition and the local fracture situation allow it.

Clinical outcome and osteoarthritic changes after surgical treatment of isolated capitulum humeri fractures with a minimum follow-up of five years.

PURPOSE: The aim of this study was to evaluate the functional outcome of patients treated for a fracture of the capitulum humeri and to analyze the grade of osteoarthritic changes. METHODS: Patients undergoing surgical reconstruction of isolated capitulum humeri fractures were included in a retrospective comparative analysis. Fractures were classified according to the Arbeitsgemeinschaft für Osteosynthesefragen (AO) and Dubberley and were functionally evaluated by the American Shoulder and Elbow Surgeons Score (ASES) and the Mayo Elbow Performance Index (MEPI). Levels of arthritic changes were measured with the Broberg and Morrey Score. Frequency of complications was evaluated whereby all results were compared to the ipsilateral, unaffected side. RESULTS: Thirteen patients, ten females (76.9 %) and three males (23.1 %), with a mean age of 48.7 ± 13.3 years were included in the study. Long-term follow-up range of motion (ROM) in the sagittal plane was significantly influenced by time of surgery (p < 0.001), and long-term follow-up with respect to pronation and supination by ROM of the healthy control (p < 0.05). The average ASES score was 37.8, and the Mayo Elbow Performance Index (MEPI) was 92.7. The mean level of degenerative arthritic changes was 1.9 ± 0.6 on the fractured side and significantly less (0.8 ± 0.8) on the healthy side (pF-test < 0.001). At a mean follow-up of 118.5 ± 52.4 months neither nonunion nor avascular necrosis were observed in any case. However, six cases of heterotopic ossification were identified. CONCLUSIONS: Satisfying functional outcomes and a low rate of osteoarthritic changes can be expected after the presented open reduction and internal fixation of capitulum humeri fractures. LEVEL OF EVIDENCE: Level IV - Case series; therapeutic study.

Treatment of proximal humerus fractures in children and young adolescents.

BACKGROUND: Fractures of the proximal humerus in children are rare and represent approximately 0.45% of all paediatric fractures. These injuries are common in patients up to an age of 16 years. The treatment of displaced subcapital fractures is still controversially discussed in literature. Therefore the aim of this study was to evaluate the short-term outcome and to provide guidelines for surgical treatment of these fractures in children and adolescents. METHODS: Clinical and radiological results of 231 patients between 0 and 17 years with subcapital humerus fractures were evaluated. Patients were devided according to their treatment as followed (1) conservative treatment group (2) operative treatment group. RESULTS: A total of 191 patients (82.7%) underwent conservative treatment and 40 (17.3%) underwent operative treatment. Surgical treatment consisted of open reduction and internal fixation (ORIF) (35.0%) or closed reduction and internal fixation (CRIF) (52.5%). In all operated patients an axial deviation of more than 20° was observed preoperatively. According to our groups; the surgical group presented in 90% (N = 36) of the patients with an excellent result, in 5% (N = 2) an average result was observed and in 5% (N = 2) a poor result according to Constant Murley Score was achieved. In the conservative treatment group in 185 patients (96.9%) excellent results were achieved and in 6 patients (3.1%) an average result in the Constant Murley Score was achieved. CONCLUSION: Conservative treatment in children < 10 years and an angulation angle < 20°, as well as surgical treatment with ORIF or CRIF in patients > 10 years and with an angulation angle > 20° leads to excellent short-term outcome. However, studies with longer observation time are needed to evaluate long-term complications like limb length discrepancy.

Tracheostomy following anterior cervical spine fusion in trauma patients.

PURPOSE: Traumatic injuries to the cervical spine are frequently accompanied by cervical spinal cord injuries-often necessitating tracheostomy. The purpose of this study was to evaluate patient characteristics and outcomes after undergoing anterior cervical spine fusion (ACSF) with tracheostomy. METHODS: All patients with cervical spine injury (CSI) who underwent ACSF and tracheostomy between December 1992 and June 2014 were included in this retrospective data analysis. The study group consisted of 32 men (84 %) and six women (16 %), with an average age of 47 ± 20 years. Blunt trauma to the cervical spine was the cause of CSI in all 38 patients. RESULTS: The mean Injury Severity Score (ISS) was 30.50 ± 6.25. Eighteen patients sustained severe concomitant injuries related to the spinal injury. In 15 patients (39.5 %), traumatic brain injury (TBI) with fractures of the cranium and/or intracranial lesions were observed. The mean Glasgow Coma Scale (GCS) score was 11 ± 4.5 (range 3-15). Two tracheostomies (5.3 %) were performed simultaneously with ACSF. The remaining 36 were performed with an average "delay" of 15 ± ten days. We observed no difference in time to tracheostomy among patients initially presenting with an American Spinal Injury Association (ASIA) score of either A, B, C or D. Only two patients (5.3 %) were identified as having an infection at the site of ACSF after placement of a tracheostomy. There were no deaths directly related to airway difficulties in our cohort. CONCLUSIONS: Our data show that tracheostomy is safely performed after an average of 15 days post-ACSF, thereby being associated with a very low rate of complications. However, future prospective randomised studies are needed to identify the optimal timing of tracheostomy placement after ACSF. LEVEL OF EVIDENCE: IV; retrospective case series.

The Difference between Growth Factor Expression after Single and Multiple Fractures: Preliminary Results in Human Fracture Healing.

OBJECTIVES: Circulating levels of VEGF-A (Vascular Endothelia Growth Factor-A), TGF-ß1 (Transforming Growth Factor-beta 1), and M-CSF (Macrophage-Colony Stimulating Factor) were found to be predictors of bone healing and therefore prognostic criteria of delayed bone healing or nonunion. The aim of this study was to evaluate a potential rise of these markers in patients with multiple fractures of long bones compared to patients with single fractured long bone. METHODS: 92 patients were included in the study and finally after excluding all female patients 45 male patients were left for final analysis and divided into the single or multiple fracture group. TGF-ß1, M-CSF, and VEGF-A serum levels were analysed over a time period of two weeks. RESULTS: MCSF serum concentrations were higher in the group with multiple fractures as also TGF-ß1 serum concentrations were at one and two weeks after trauma. No statistically significant difference was observed in the VEGF-A serum concentrations of both groups at either measurement point. CONCLUSION: We did observe a correlation between the quantity of the M-CSF and TGF-ß1 expressions in serum and the number of fractured bones; surprisingly there was no statistically significant difference in the serum levels between patients with single and multiple fractures of long bones.

An Analytical Comparison of the Opinions of Physicians Working in Emergency and Trauma Surgery Departments at Tabriz and Vienna Medical Universities Regarding Family Presence during Resuscitation.

The present study evaluated the opinions of physicians working in the emergency and trauma surgery departments of Vienna Medical University, in Austria, and Tabriz Medical University, in Iran, regarding the presence of patients' relatives during resuscitation. In a descriptive-analytical study, the data obtained from questionnaires that had been distributed randomly to 40 specialists and residents at each of the participating universities were analyzed. The questionnaire consisted of two sections aimed at capturing the participants' demographic data, the participants' opinions regarding their support for the family's presence during resuscitation, and the multiple potential factors affecting the participants' attitudes, including health beliefs, triggers that could facilitate the procedure, self-efficacy, intellectual norms, and perceived behavioral control. The questionnaire also included a direct question (Question 16) on whether the participants approved of family presence. Each question could be answered using a Likert-type scale. The results showed that the mean scores for Question 16 were 4.31 ± 0.64 and 3.57 ± 1.31 for participants at Vienna and Tabriz universities, respectively. Moreover, physicians at Vienna University disapproved of the presence of patients' families during resuscitation to a higher extent than did those at Tabriz University (P = 0.018). Of the studied prognostic factors affecting the perspectives of Vienna Medical University's physicians, health beliefs (P = 0.000; B = 1.146), triggers (P = 0.000; B = 1.050), and norms (P = 0.000; B = 0.714) were found to be significant. Moreover, of the studied prognostic factors affecting the perspectives of Tabriz Medical University's physicians, health beliefs (P = 0.000; B = 0.875), triggers (P = 0.000; B = 1.11), self-efficacy (P = 0.001; B = 0.5), and perceived behavioral control (P = 0.03; B = 0.713) were significant. Most physicians at Vienna and Tabriz Medical universities were not open towards family members' presence during resuscitation.

Analysis of S100 calcium binding protein B serum levels in different types of traumatic intracranial lesions.

The objective of this study was to determine whether the type of intracranial traumatic lesions, the number of simultaneous traumatic lesions, and the occurrence of skull and facial bone fractures have an influence on S100 calcium binding protein B (S100B) serum levels. Patients with blunt traumatic brain injury were prospectively enrolled into this cohort study over a period of 13 months. Venous blood samples were obtained prior to emergency cranial CT scan in all patients within 3 h after injury. The patients were then assigned into six groups: 1) concussion, 2) epidural hematoma, 3) subdural hematoma, 4) subarachnoid hemorrhage, 5) brain contusions, and 6) brain edema. The study included 1696 head trauma patients with a mean age of 57.7 ± 25.3 years, and 126 patients (8%) had 182 traumatic lesions on CT. Significant differences in S100B serum levels were found between cerebral edema and the other four bleeding groups: epidural p = 0.0002, subdural p < 0.0001, subarachnoid p = 0.0001, brain contusions p = 0.0003, and concussion p < 0.0001. Significant differences in S100B values between patients with one or two intracranial lesions (p = 0.014) or with three (p < 0.0001) simultaneous intracranial lesions were found. In patients with intracranial traumatic lesions, skull fractures, as well as skull and facial bone fractures occurring together, were identified as significant additional factors for the increase in serum S100B levels (p < 0.0001). Older age was also associated with elevated S100B serum levels (p < 0.0001). Our data show that peak S100B serum levels were found in patients with cerebral edema and brain contusions.

Is sonic Hedgehog involved in human fracture healing? --a prospective study on local and systemic concentrations of SHH.

INTRODUCTION: Sonic Hedgehog (SHH) is a new signalling pathway in bone repair. Evidence exist that SHH pathway plays a significant role in vasculogenesis and limb development during embryogenesis. Some in vitro and animal studies has already proven its potential for bone regeneration. However, no data on the role of SHH in the human fracture healing have been published so far. METHODS: Seventy-five patients with long bone fractures were included into the study and divided in 2 groups. First group contained 69 patients with normal fracture healing. Four patients with impaired fracture healing formed the second group. 34 volunteers donated blood samples as control. Serum samples were collected over a period of 1 year following a standardized time schedule. In addition, SHH levels were measured in fracture haematoma and serum of 16 patients with bone fractures. RESULTS: Fracture haematoma and patients serum both contained lower SHH concentrations compared to control serum. The comparison between the patients' serum SHH level and the control serum revealed lower levels for the patients at all measurement time points. Significantly lower concentrations were observed at weeks 1 and 2 after fracture. SHH levels were slightly decreased in patients with impaired fracture healing without statistical significance. CONCLUSION: This is the first study to report local and systemic concentration of SHH in human fracture healing and SHH serum levels in healthy adults. A significant reduction of the SHH levels during the inflammatory phase of fracture healing was found. SHH concentrations in fracture haematoma and serum were lower than the concentration in control serum for the rest of the healing period. Our findings indicate that there is no relevant involvement of SHH in human fracture healing. Fracture repair process seem to reduce the SHH level in human. Further studies are definitely needed to clarify the underlying mechanisms.

Are OPG and RANKL involved in human fracture healing?

Human fracture healing is a complex interaction of several cytokines that regulate osteoblast and osteoclast activity. By monitoring OPG (osteoprotegerin) and sRANKL we aimed to possibly predict normal or impaired fracture healing. In 64 patients with a fracture of a long bone serum level of sRANKL and OPG were evaluated with respect to bony union (n=57) or pseudarthrosis (n=7). Measurements were carried out at admission and at 1, 2, 4, 6, 8, 12, 24, and 48 weeks after the injury. Patients' serum levels were compared to 33 healthy controls. Fracture hematoma contained significantly higher sRANKL and OPG concentrations compared to patients serum (p=0.005, p=0.028). OPG level in fracture hematoma was higher compared to the unions serum level (p=0.028). sRANKL was decreased in unions during the observation period. In non-unions sRANKL and OPG levels showed a variable course, with no statistical significance. This is the first study to document the course of OPG and sRANKL in normal and delayed human fracture healing emphasizing its local and systemic involvement. We provide evidence of strongly enhanced OPG levels in patients with a long bone fracture compared to healthy controls. Further, levels of free sRANKL were decreased during regular fracture repair.