Validation of the AO Spine Sacral Classification System: Reliability Among Surgeons Worldwide.

OBJECTIVES: To (1) demonstrate that the AO Spine Sacral Classification System can be reliably applied by general orthopaedic surgeons and subspecialists universally around the world and (2) delineate those injury subtypes that are most difficult to classify reliably to refine the classification before evaluating clinical outcomes. DESIGN: Agreement study. SETTING: All-level trauma centers, worldwide. PARTICIPANTS: One hundred seventy-two members of the AO Trauma and AO Spine community. INTERVENTION: The AO Sacral Classification System was applied by each surgeon to 26 cases in 2 independent assessments performed 3 weeks apart. MAIN OUTCOME MEASUREMENTS: Interobserver reliability and intraobserver reproducibility. RESULTS: A total of 8097 case assessments were performed. The kappa coefficient for interobserver agreement for all cases was 0.72/0.75 (assessment 1/assessment 2), representing substantial reliability. When comparing classification grading (A/B/C) regardless of subtype, the kappa coefficient was 0.84/0.85, corresponding to excellent reliability. The kappa coefficients for interobserver reliability were 0.95/0.93 for type A fractures, 0.78/0.79 for type B fractures, and 0.80/0.83 for type C fractures. The overall kappa statistic for intraobserver reliability was 0.82 (range 0.18-1.00), representing excellent reproducibility. When only evaluating morphology type (A/B/C), the average kappa value was 0.87 (range 0.18-1.00), representing excellent reproducibility. CONCLUSION: The AO Spine Sacral Classification System is universally reliable among general orthopaedic surgeons and subspecialists worldwide, with substantial interobserver and excellent intraobserver reliability.

Description and Reliability of the AOSpine Sacral Classification System.

BACKGROUND: Several classification systems exist for sacral fractures; however, these systems are primarily descriptive, are not uniformly used, have not been validated, and have not been associated with a treatment algorithm or prognosis. The goal of the present study was to demonstrate the reliability of the AOSpine Sacral Classification System among a group of international spine and trauma surgeons. METHODS: A total of 38 sacral fractures were reviewed independently by 18 surgeons selected from an expert panel of AOSpine and AOTrauma members. Each case was graded by each surgeon on 2 separate occasions, 4 weeks apart. Intrarater reproducibility and interrater agreement were analyzed with use of the kappa statistic (κ) for fracture severity (i.e., A, B, and C) and fracture subtype (e.g., A1, A2, and A3). RESULTS: Seventeen reviewers were included in the final analysis, and a total of 1,292 assessments were performed (646 assessments performed twice). Overall intrarater reproducibility was excellent (κ = 0.83) for fracture severity and substantial (κ = 0.71) for all fracture subtypes. When comparing fracture severity, overall interrater agreement was substantial (κ = 0.75), with the highest agreement for type-A fractures (κ = 0.95) and the lowest for type-C fractures (κ = 0.70). Overall interrater agreement was moderate (κ = 0.58) when comparing fracture subtype, with the highest agreement seen for A2 subtypes (κ = 0.81) and the lowest for A1 subtypes (κ = 0.20). CONCLUSIONS: To our knowledge, the present study is the first to describe the reliability of the AOSpine Sacral Classification System among a worldwide group of expert spine and trauma surgeons, with substantial to excellent intrarater reproducibility and moderate to substantial interrater agreement for the majority of fracture subtypes. These results suggest that this classification system can be reliably applied to sacral injuries, providing an important step toward standardization of treatment.

Autologous Transplantation of Press-fit Bone Cylinders in the Treatment of Pelvic Nonunion.

The present study describes method for autologous bone transplantation to an area of nonunion at the pelvic ring in a way that ensures the best possible bone-to-bone interface ("press-fit") and provides optimal preconditions for the ingrowth of the bone graft. We modified a technique that has been used to transplant press-fit bone-baseplate-cartilage cylinders for the repair of joint cartilage defects. The technique allows for precise harvesting of bone cylinders with a diamond-coated and fluid-cooled instrument. At the site where the graft shall be inserted, a cylindrical hole is created with a corresponding hollow diamond-coated trephine. This ensures an optimal press-fit implantation of the graft. The new surgical technique has been applied in four patients with nonunion of the pelvic ring. No intraoperative or postoperative complications occurred. In three patients, the procedure led to a reduction of pain and a higher level of mobility as well as a timely radiographic union (imaging not available for another patient). Our technique offers a valuable new treatment option for pelvic nonunion. The current article serves as a proof of concept. Future comparative studies will have to determine its value in detail.

VEGF-loaded mineral-coated microparticles improve bone repair and are associated with increased expression of epo and RUNX-2 in murine non-unions.

A poor vascular supply of the fracture gap is a key factor for the development of atrophic non-unions. Mineral-coated microparticles (MCM) represent a sophisticated carrier system for the delivery of vascular endothelial growth factor (VEGF). Hence, we investigated whether VEGF-loaded MCM improve bone repair in non-unions. For this purpose, we analyzed binding and release kinetics of MCM for VEGF in vitro. Moreover, we applied VEGF-loaded or -unloaded MCM in a murine non-union model in vivo and studied the process of bone healing by means of biomechanical, radiological, histomorphometric, and Western blot techniques. MCM-free non-unions served as controls. The binding efficiency of MCM for VEGF was 46 ± 3% and the release profile revealed an initial minor burst release followed by a sustained release over a 50-day study period, thus, mimicking the physiological expression profile of VEGF during bone healing. In vivo, bone defects treated with VEGF-loaded MCM exhibited a higher bending stiffness, a higher fraction of bone volume/tissue volume and a larger callus area on days 14 and 70 when compared to the other groups. Western blot analyses on day 14 revealed a higher expression of VEGF, erythropoietin (EPO), and runt-related transcription factor 2, but not of EPO-receptor in bone defects treated with VEGF-loaded MCM. These findings demonstrate that the use of MCM for VEGF delivery shows great potential due to the ability to maintain protein stability and functionality in vivo. Moreover, the application of VEGF-loaded MCM represent a promising strategy for the treatment of non-unions. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Geriatric Acetabular Surgery: Letournel's Contraindications Then and Now-Data From the German Pelvic Registry.

OBJECTIVE: In his original series of 129 surgically treated acetabular fractures, Letournel did not operate on patients older than 60 years. Almost 30 years later, he still emphasized that no patients with reduced bone quality should be operated on. The aim of the study was to analyze epidemiologic characteristics and treatment modes for today's cohort of elderly patients with acetabular fractures. DESIGN: Retrospective analysis. SETTING: Multicenter registry/Level I trauma center. PATIENTS: Three thousand seven hundred ninety-three patients who had sustained a fracture of the acetabulum. INTERVENTION: Operative and nonoperative treatment of acetabular fractures. MAIN OUTCOME MEASUREMENTS: Epidemiologic characteristics, treatment mode, in-hospital mortality, rate of secondary hip arthroplasty, and quality of life indicated by EQ-5D score. RESULTS: For the multicenter registry, more than 50% of all patients with acetabular fractures had an age of 60 years or over. The age peak was found at 75-80 years. Fifty percent of the elderly patients were treated surgically. The in-hospital mortality was significantly higher in elderly patients than patients younger than 60 years. In our Level I trauma center, surgical treatment by open reduction and internal fixation did not influence in-hospital mortality or quality of life of elderly patients with acetabular fractures. CONCLUSIONS: Today, elderly persons represent the dominant cohort among patients with fractures of the acetabulum. Fifty-five years after the publication of Letournel's original case series, data indicate that currently, surgical treatment is a common and necessary option in the therapy of acetabular fractures in elderly patients. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Predictors for secondary hip osteoarthritis after acetabular fractures-a pelvic registry study.

PURPOSE: Secondary hip osteoarthritis after acetabular fractures requiring total arthroplasty (THA) poses a huge burden on the affected patients as well as health systems. The present study aimed to assess risk factors associated with THA after acetabular fractures based on the data from the German Pelvic Trauma Registry. METHODS: Retrospective analysis of 678 acetabular fracture cases without concomitant pelvic ring fracture treated and followed-up between January 2004 and May 2015 at six large trauma centres. Multivariate Cox regression analysis was performed assessing the association of patient/treatment characteristics with THA likelihood at an average follow-up of 2.7 years (range 0.4-9.5 years; SD 1.8 years). RESULTS: Overall, the rate of secondary osteoarthritis was 19.8%. The likelihood for THA increased with 6% per age year (95% CI 1.04-1.09) and with 21% per millimetre subluxation (95%CI 1.09-1.33). This likelihood was 3.54 (95% CI 1.77-7.08) and 3.68 times (95% CI 1.87-7.47) higher if the posterior wall was involved and a contusion and/or impaction of the femoral head was present. Other covariates (sex, ISS, trauma type, AO/OTA and Letournel classification, initial displacement, surgical approach, intra-articular fragments, contusion and/or impaction to the acetabulum, reduction, intervention type, duration of surgery, soft tissue damage, residual fracture step/gap, and prevention of heterotopic ossifications) were not significantly associated (p > 0.15). CONCLUSIONS: Twenty percent of patients with acetabular fractures require THA. The associated risk factors are patient age, femoral head lesion/subluxation, and involvement of the posterior wall. The identified risk factors support previous research and should be minded when treatment of acetabular fractures is planned.

Marble-derived microcalcite improves bone healing in mice osteotomy.

Approximately 10% of all fractures result in delayed healing or non-unions. Bone healing can be improved by the application of osteoconductive and osteoinductive biomaterials. Microcalcite (MCA) as a naturally available calcium carbonate-based biomaterial derived from marble may have the potential to improve bone healing. Herein, we studied for the first time, if MCA in combination with platelet-rich plasma (PRP) can be used as a bone graft material for bone healing in vivo. For this purpose, osteotomies were induced in CD-1 mice (n = 60). Animals received into the osteotomy gap either MCA-loaded PRP (MCA + PRP; n = 20), PRP alone (PRP; n = 20) or no application (NONE; n = 20). Bone healing was evaluated at two and five weeks after osteotomy by micro-computed tomography (µCT), histomorphometric, immunohistochemical and Western Blot analyses. µCT of MCA + PRP femurs revealed more bone volume and an increased polar moment of inertia, indicating a higher biomechanical stability when compared to PRP and NONE femurs. Histomorphometry revealed an increased total callus area after two weeks and a reduced callus tissue area after five weeks in MCA + PRP and PRP animals compared to NONE animals, indicating an accelerated process of bone healing and remodeling over the study period. Moreover, histomorphometric analyses demonstrated an increased fraction of osseous tissue within the callus in MCA + PRP femurs when compared to PRP and NONE femurs. Immunohistochemical analyses showed increased numbers of Ki67+ cells in callus tissue of MCA + PRP femurs. Of interest, Western Blotting revealed a significantly reduced expression of BMP-4 in MCA + PRP animals, while the expression of BMP-2 did not reveal any significant differences between the groups. This indicates a modified balance between angiogenesis and osteogenesis due to MCA. In conclusion, the application of MCA with PRP improved bone healing in a murine osteotomy model and, thus, might be a promising novel bone graft material which may be of interest for clinical fracture treatment.

Long-term pathological gait pattern changes after talus fractures - dynamic measurements with a new insole.

PURPOSE: The aim of the current study was to describe long-term gait changes after talus fractures, identify patterns associated with poor outcome and discuss possible treatment options based on dynamic gait analysis. METHODS: Twenty-seven patients were followed-up clinically and via gait analysis after talus fracture osteosynthesis. Continuous dynamic pedobarography with a gait analysis insole was performed on a standardized parcours consisting of different gait tasks and matched to the outcome. RESULTS: Mean follow-up was 78.3 months (range 21-150), mean AOFAS and Olerud-Molander scores 66 (range 20-100) and 54 (range 15-100). Significant correlations between fracture classification and osteoarthritis (Hawkins: rs = 0.67 / Marti-Weber: rs = 0.5) as well as several gait differences between injured and healthy foot with correlations to outcome were seen: decreased step load-integral/maximum-load; associations between centre-of-pressure displacement and outcome as well as between temporospatial measures and outcome. Overall, pressure-distribution was lateralized in patients with subtalar joint injury (Δ: 0.5765 N/cm2, p = 0.0475). CONCLUSIONS: Talus fractures lead to chronic gait changes and restricted function. Dynamic pedobarography can identify patterns associated with poor results. The observed gait patterns suggest that changes can be addressed by physical therapy and customized orthoses to improve overall outcome. The presented insole and measurement protocol are immediately feasible as a diagnostic and rehabilitation aid.

Sacral Fractures and Associated Injuries.

STUDY DESIGN: Literature review. OBJECTIVE: The aim of this review is to describe the injuries associated with sacral fractures and to analyze their impact on patient outcome. METHODS: A comprehensive narrative review of the literature was performed to identify the injuries associated with sacral fractures. RESULTS: Sacral fractures are uncommon injuries that result from high-energy trauma, and that, due to their rarity, are frequently underdiagnosed and mistreated. Only 5% of sacral fractures occur in isolation. Injuries most often associated with sacral fractures include neurologic injuries (present in up to 50% of sacral fractures), pelvic ring disruptions, hip and lumbar spine fractures, active pelvic/ abdominal bleeding and the presence of an open fracture or significant soft tissue injury. Diagnosis of pelvic ring fractures and fractures extending to the lumbar spine are key factors for the appropriate management of sacral fractures. Importantly, associated systemic (cranial, thoracic, and abdominopelvic) or musculoskeletal injuries should be promptly assessed and addressed. These associated injuries often dictate the management and eventual outcome of sacral fractures and, therefore, any treatment algorithm should take them into consideration. CONCLUSIONS: Sacral fractures are complex in nature and often associated with other often-missed injuries. This review summarizes the most relevant associated injuries in sacral fractures and discusses on their appropriate management.

Mechanical and biological characterization of alkaline substituted orthophosphate bone substitutes containing meta- and diphosphates.

Despite the growing knowledge on the mechanisms of fracture healing, bone defects often do not heal in a timely manner. Clinically, tricalcium phosphate (TCP) bone substitutes are used to fill bone defects and promote bone healing. However, the degradation rate of these implants is often too slow for sufficient bone replacement. The use of calcium phosphate material with the crystalline phase Ca10[K/Na](PO4)7 containing different amounts of di- and metaphosphates may overcome this problem, because these materials show an accelerated degradation. Therefore, we generated alkaline substituted Ca-P scaffolds with different amounts of ortho-, di- and metaphosphates. The degradation of these materials was analyzed in TRIS-HCl buffer solution in vitro. Moreover, we measured the compressive strength and porosity of the scaffolds by micro-CT analysis. The biocompatibility of the scaffolds was evaluated in vivo in the mouse dorsal skinfold chamber by means of intravital fluorescence microscopy and histology. We found that higher amounts of incorporated di- and metaphosphates increase the degradation rate and compressive strength of the scaffolds without inducing a stronger leukocytic inflammatory host tissue reaction after implantation. Histological analyses confirmed the good biocompatibility of the scaffolds containing di- and metaphosphates. In summary, this study demonstrates that the compressive strength and degradation rate of Ca-P scaffolds can be improved by incorporation of di- and metaphosphates without affecting their good biocompatibility. Hence, this material modification may be particularly beneficial for the treatment of metaphyseal bone defects in weight bearing locations.

Weight-bearing recommendations after operative fracture treatment-fact or fiction? Gait results with and feasibility of a dynamic, continuous pedobarography insole.

PURPOSE: Rehabilitation after lower-extremity fractures is based on the physicians' recommendation for non-, partial-, or full weight-bearing. Clinical studies rely on this assumption, but continuous compliance or objective loading rates are unknown. The purpose of this study was to determine the compliance to weight-bearing recommendations by introducing a novel, pedobarography system continuously registering postoperative ground forces into ankle, tibial shaft and proximal femur fracture aftercare and test its feasibility for this purpose. METHODS: In this prospective, observational study, a continuously measuring pedobarography insole was placed in the patients shoe during the immediate post-operative aftercare after ankle, tibial shaft and intertrochanteric femur fractures. Weight-bearing was ordered as per the institutional standard and controlled by physical therapy. The insole was retrieved after a maximum of six weeks (28 days [range 5-42 days]). Non-compliance was defined as a failure to maintain, or reach the ordered weight-bearing within 30%. RESULTS: Overall 30 patients were included in the study. Fourteen (47%) of the patients were compliant to the weight-bearing recommendations. Within two weeks after surgery patients deviated from the recommendation by over 50%. Sex, age and weight did not influence the performance (p > 0.05). Ankle fracture patients (partial weight-bearing) showed a significantly increased deviation from the recommendation (p = 0.01). CONCLUSIONS: Our study results show that, despite physical therapy training, weight-bearing compliance to recommended limits was low. Adherence to the partial weight-bearing task was further decreased over time. Uncontrolled weight-bearing recommendations should thus be viewed with caution and carefully considered as fiction. The presented insole is feasible to determine weight bearing continuously, could immediately help define real-time patient behaviour and establish realistic, individual weight-bearing recommendations.

Predictive value of clinical scoring and simplified gait analysis for acetabulum fractures.

BACKGROUND: Fractures of the acetabulum show a high, long-term complication rate. The aim of the present study was to determine the predictive value of clinical scoring and standardized, simplified gait analysis on the outcome after these fractures. METHODS: Forty-one patients with acetabular fractures treated between 2008 and 2013 and available, standardized video recorded aftercare were identified from a prospective database. A visual gait score was used to determine the patients walking abilities 6-m postoperatively. Clinical (Merle d'Aubigne and Postel score, visual analogue scale pain, EQ5d) and radiological scoring (Kellgren-Lawrence score, postoperative computed tomography, and Matta classification) were used to perform correlation and multivariate regression analysis. RESULTS: The average patient age was 48 y (range, 15-82 y), six female patients were included in the study. Mean follow-up was 1.6 y (range, 1-2 y). Moderate correlation between the gait score and outcome (versus EQ5d: rs = 0.477; versus Merle d'Aubigne: rs = 0.444; versus Kellgren-Lawrence: rs = -0.533), as well as high correlation between the Merle d'Aubigne score and outcome were seen (versus EQ5d: rs = 0.575; versus Merle d'Aubigne: rs = 0.776; versus Kellgren-Lawrence: rs = -0.419). Using a multivariate regression model, the 6 m gait score (B = -0.299; P < 0.05) and early osteoarthritis development (B = 1.026; P < 0.05) were determined as predictors of final osteoarthritis. A good fit of the regression model was seen (R2 = 904). CONCLUSIONS: Easy and available clinical scoring (gait score/Merle d'Aubigne) can predict short-term radiological and functional outcome after acetabular fractures with sufficient accuracy. Decisions on further treatment and interventions could be based on simplified gait analysis.

Stimulation of angiogenesis by cilostazol accelerates fracture healing in mice.

Cilostazol, a selective phosphodiesterase-3 inhibitor, is known to control cyclic adenosine monophosphate (c-AMP) and to stimulate angiogenesis through upregulation of pro-angiogenic factors. There is no information, however, whether cilostazol affects fracture healing. We, therefore, studied the effect of cilostazol on callus formation and biomechanics during fracture repair. Bone healing was analyzed in a murine femur fracture stabilized with an intramedullary screw. Radiological, biomechanical, histomorphometric, histochemical, and protein biochemical analyses were performed at 2 and 5 weeks after fracture. Twenty-five mice received 30 mg/kg body weight cilostazol p.o. daily. Controls (n=24) received equivalent amounts of vehicle. In cilostazol-treated animals radiological analysis at 2 weeks showed an improved healing with an accelerated osseous bridging compared to controls. This was associated with a significantly higher amount of bony tissue and a smaller amount of cartilage tissue within the callus. Western blot analysis showed a higher expression of cysteine-rich protein 61 (CYR61), bone morphogenetic protein (BMP)-4, and receptor activator of NF-kappaB ligand (RANKL). At 5 weeks, improved fracture healing after cilostazol treatment was indicated by biomechanical analyses, demonstrating a significant higher bending stiffness compared to controls. Thus, cilostazol improves fracture healing by accelerating both bone formation and callus remodeling.

Comparison of healing process in open osteotomy model and open fracture model: Delayed healing of osteotomies after intramedullary screw fixation.

Murine osteotomy and fracture models have become the standard to study molecular mechanisms of bone healing. Because there is little information whether the healing of osteotomies differs from that of fractures, we herein studied in mice the healing of femur osteotomies compared to femur fractures. Twenty CD-1 mice underwent a standardized open femur osteotomy. Another 20 mice received a standardized open femur fracture. Stabilization was performed by an intramedullary screw. Bone healing was studied by micro-CT, biomechanical, histomorphometric and protein expression analyses. Osteotomies revealed a significantly lower biomechanical stiffness compared to fractures. Micro-CT showed a reduced bone/tissue volume within the callus of the osteotomies. Histomorphometric analyses demonstrated also a significantly lower amount of osseous tissue in the callus of osteotomies (26% and 88% after 2 and 5 weeks) compared to fractures (50% and 100%). This was associated with a delayed remodeling. Western blot analyses demonstrated comparable BMP-2 and BMP-4 expression, but higher levels of collagen-2, CYR61 and VEGF after osteotomy. Therefore, we conclude that open femur osteotomies in mice show a markedly delayed healing when stabilized less rigidly with an intramedullary screw. This should be considered when choosing a model for studying the mechanisms of bone healing in mice.

Compression and contact area of anterior strut grafts in spinal instrumentation: a biomechanical study.

BACKGROUND: Anterior bone grafts are used as struts to reconstruct the anterior column of the spine in kyphosis or following injury. An incomplete fusion can lead to later correction losses and compromise further healing. Despite the different stabilizing techniques that have evolved, from posterior or anterior fixating implants to combined anterior/posterior instrumentation, graft pseudarthrosis rates remain an important concern. Furthermore, the need for additional anterior implant fixation is still controversial. In this bench-top study, we focused on the graft-bone interface under various conditions, using two simulated spinal injury models and common surgical fixation techniques to investigate the effect of implant-mediated compression and contact on the anterior graft. METHODS: Calf spines were stabilised with posterior internal fixators. The wooden blocks as substitutes for strut grafts were impacted using a "pressfit" technique and pressure-sensitive films placed at the interface between the vertebral bone and the graft to record the compression force and the contact area with various stabilization techniques. Compression was achieved either with posterior internal fixator alone or with an additional anterior implant. The importance of concomitant ligament damage was also considered using two simulated injury models: pure compression Magerl/AO fracture type A or rotation/translation fracture type C models. RESULTS: In type A injury models, 1 mm-oversized grafts for impaction grafting provided good compression and fair contact areas that were both markedly increased by the use of additional compressing anterior rods or by shortening the posterior fixator construct. Anterior instrumentation by itself had similar effects. For type C injuries, dramatic differences were observed between the techniques, as there was a net decrease in compression and an inadequate contact on the graft occurred in this model. Under these circumstances, both compression and the contact area on graft could only be maintained at high levels with the use of additional anterior rods. CONCLUSIONS: Under experimental conditions, we observed that ligamentous injury following type C fracture has a negative influence on the compression and contact area of anterior interbody bone grafts when only an internal fixator is used for stabilization. Because of the loss of tension banding effects in type C injuries, an additional anterior compressing implant can be beneficial to restore both compression to and contact on the strut graft.

Development of a reliable non-union model in mice.

BACKGROUND: Despite the growing knowledge of the mechanisms of fracture healing, non-unions remain a substantial clinical problem. There is increasing interest in murine fracture models because they would allow studying molecular mechanisms of healing with the help of specific antibodies and gene-targeted animals. However, until now it has not been possible to reproducibly create non-unions in mice. Thus, the aim of this study was to develop a reliable non-union model in mice. METHODS: After creating segmental defects of 0.8 mm and 1.8 mm, mice femora were stabilized with a pin-clip fixation. Additionally, the influence of periosteal resection on the development of non-unions was studied. Histological and radiological healing was analyzed 5, 10, and 15 wk after surgery. RESULTS: After 10 wk all animals showed poor healing with predominantly atrophic non-unions. Whereas the 0.8 mm and the 1.8 mm gap with intact periosteum showed radiologically in 4/6 and 3/6 cases possible healing, only the gap of 1.8 mm with additional periosteal resection resulted in 100% (6/6) non-unions. The non-unions were confirmed also after 15 wk and appeared atrophic with typical histological and radiological features. These included lack of fracture bridging with abundant fibrous tissue in the gap, absence of callus formation, and rounded bone ends. Of interest, the non-unions were not avascular, but demonstrated a considerable vascularity within the fibrous tissue. CONCLUSION: Taken together, we herein demonstrate for the first time a reliable non-union model in mice. This allows us to study molecular aspects of non-union formation and analyze different therapeutical strategies in these animals.