Jörg H. Holstein

Different stabilisation techniques for typical acetabular fractures in the elderly—A biomechanical assessment

OBJECTIVES The tremendous increase of acetabular fractures in the elderly provides new challenges for their surgical treatment. The aim of this study was to evaluate the biomechanical properties of conventional and newly developed implants for the stabilisation of an anterior column combined with posterior hemitransverse fracture (ACPHTF), which represents the typical acetabular fracture in the elderly. METHODS Using a single-leg stance model we analysed four different implant systems for the stabilisation of ACPHTFs in synthetic and cadaveric pelvises. Applying an increasing axial load, fracture dislocation was analysed with a new multidirectional ultrasonic measuring system. Results of the different implant systems were compared by Scheffé post hoc test and one-way ANOVA. RESULTS In synthetic pelvises, the standard reconstruction plate fixed by 3 periarticular long screws and a new titanium fixator with multidirectional interlocking screws were associated with significantly less dislocation of the fractured quadrilateral plate of the acetabulum when compared to a standard reconstruction plate fixed by only one periarticular long screw and a locking reconstruction plate. No significant differences between the different osteosynthesis techniques could be observed in cadaver pelvises, probably due to a heterogeneous bone quality. CONCLUSIONS We conclude that the plate fixation by positioning of periarticular long screws as well as the multidirectional positioning of interlocking screws account for the most sufficient fracture stabilisation of ACPHTFs under experimental conditions.

Emergency stabilization of the pelvic ring: Clinical comparison between three different techniques

BACKGROUND Emergency devices for pelvic ring stabilization include circumferential sheets, pelvic binders, and c-clamps. Our knowledge of the outcome of these techniques is currently based on limited information. METHODS Using the dataset of the German Pelvic Trauma Registry, demographic and injury-associated characteristics as well as the outcome of pelvic fracture patients after sheet, binder, and c-clamp treatment was compared. Outcome parameters included transfusion requirement of packed red blood cells, length of hospital stay, mortality, and incidence of lethal pelvic bleeding. RESULTS Two hundred seven of 6137 (3.4%) patients documented in the German Pelvic Trauma Registry between April 30th 2004 and January 19th 2012 were treated by sheets, binders, or c-clamps. In most cases, c-clamps (69%) were used, followed by sheets (16%), and binders (15%). The median age was significantly lower in patients treated with binders than in patients treated with sheets or c-clamps (26 vs. 47 vs. 42 years, p=0.01). Sheet wrapping was associated with a significantly higher incidence of lethal pelvic bleeding compared to binder or c-clamp stabilization (23% vs. 4% vs. 8%). No significant differences between the study groups were found in sex, fracture type, blood haemoglobin concentration, arterial blood pressure, Injury Severity Score, the incidence of additional pelvic packing and arterial embolization, need of red blood cell transfusion, length of hospitalisation, and mortality. CONCLUSIONS The data suggest that emergency stabilization of the pelvic ring by binders and c-clamps is associated with a lower incidence of lethal pelvic bleeding compared to sheet wrapping. LEVEL OF EVIDENCE Level III.

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.

Obesity does not affect the healing of femur fractures in mice.

Obesity is reported to be both protective and deleterious to bone. Lipotoxicity and inflammation might be responsible for bone loss through inhibition of osteoblasts and activation of osteoclasts. However, little is known whether obesity affects the process of fracture healing. Therefore, we studied the effect of high fat diet-induced (HFD) obesity on callus formation and bone remodelling in a closed femur fracture model in mice. Thirty-one mice were fed a diet containing 60kJ% fat (HFD) for a total of 20 weeks before fracture and during the entire postoperative observation period. Control mice (n=31) received a standard diet containing 10kJ% fat. Healing was analyzed using micro-CT, biomechanical, histomorphometrical, immunohistochemical, serum and protein biochemical analysis at 2 and 4 weeks after fracture. HFD-fed mice showed a higher body weight and increased serum concentrations of leptin and interleukin-6 compared to controls. Within the callus tissue Western blot analyses revealed a higher expression of transcription factor peroxisome proliferator-activated receptor y (PPARy) and a reduced expression of runt-related transcription factor 2 (RUNX2) and bone morphogenetic protein (BMP)-4. However, obesity did not affect the expression of BMP-2 and did not influence the receptor activator of nuclear factor κB (RANK)/RANK ligand/osteoprotegerin (OPG) pathway during fracture healing. Although the bones of HFD-fed animals showed an increased number of adipocytes within the bone marrow, HFD did not increase callus adiposity. In addition, radiological and histomorphometric analysis could also not detect significant differences in bone formation between HFD-fed animals and controls. Accordingly, HFD did not affect bending stiffness after 2 and 4 weeks of healing. These findings indicate that obesity does not affect femur fracture healing in mice.

[Fractures of the acetabulum: complications and joint replacement].

Acetabular fractures assume a special role amongst the fractures of the pelvis, because they involve a major weight-bearing joint. As those fractures mostly result from exposure to great force, and because of their location in an anatomically complex region, a high rate of complications has to be anticipated. Besides general and perioperative complications long-term consequences, especially post-traumatic arthrosis, are relevant problems when it comes to treating fractures of the acetabulum. The primary reconstruction of the acetabulum, as well as a possibly necessary prosthetic replacement of the hip joint, makes high demands on the diagnostic and operative capabilities of the attending physician. Exact knowledge of the specific risks and pitfalls for each type of fracture and for the specific surgical techniques is crucial for a successful treatment. Due to the much worse long-term outcome when compared to primary total hip replacement in patients with osteoarthritis, acetabular fractures should, regardless of the patients age, whenever possible be treated by operative reconstruction.

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.

Comparative Degradomics of Porcine and Human Wound Exudates Unravels Biomarker Candidates for Assessment of Wound Healing Progression in Trauma Patients

Impaired cutaneous wound healing is a major complication in elderly people and patients suffering from diabetes, the rate of which is rising in industrialized countries. Heterogeneity of clinical manifestations hampers effective molecular diagnostics and decisions for appropriate therapeutic regimens. Using a customized positional quantitative proteomics workflow, we have established a time-resolved proteome and N-terminome resource from wound exudates in a clinically relevant pig wound model that we exploited as a robust template to interpret a heterogeneous dataset from patients undergoing the same wound treatment. With zyxin, IQGA1, and HtrA1, this analysis and validation by targeted proteomics identified differential abundances and proteolytic processing of proteins of epidermal and dermal origin as prospective biomarker candidates for assessment of critical turning points in wound progression. Thus, we show the possibility of using a fine-tuned animal wound model to bridge the translational gap as a prerequisite for future extended clinical studies with large cohorts of individuals affected by healing impairments. Data are available via ProteomeXchange with identifier PXD006674.

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.

Intertrochanteric Hip Fracture: Intramedullary Nails

The incidence of intertrochanteric hip fractures is expected to increase worldwide. Evidence-based approaches to treatment strategies, and surrounding support and aftercare structures, are needed to reduce morbidity and mortality in the increasingly aging and comorbid fracture population. In this chapter, relevant anatomy, biomechanics, and classification systems to determine fracture stability and consequent osteosynthetic treatment, as well as peri-operative management, are discussed. Adequate stability assessment is the key to determine the necessity for intramedullary nailing as compared to extramedullary fixation. Pearls and pitfalls of the surgical process of intramedullary nailing for intertrochanteric femur fractures are discussed, and common complications are shown. Evidence-based medical and anesthesiological management strategies during the pre-, peri-, and post-operative treatment period, as well as aftercare principals, are described.

Effects of locally applied adipose tissue-derived microvascular fragments by thermoresponsive hydrogel on bone healing

Insufficient vascularization is a major cause for the development of non-unions. To overcome this problem, adipose tissue-derived microvascular fragments (MVF) may serve as vascularization units. However, their application into bone defects needs a carrier system. Herein, we analyzed whether this is achieved by a thermoresponsive hydrogel (TRH). MVF were isolated from CD-1 mice and cultivated after incorporation into TRH, while non-incorporated MVF served as controls. Viability of MVF was assessed immunohistochemically over a 7-day period. Moreover, osteotomies were induced in femurs of CD-1 mice. The osteotomy gaps were filled with MVF-loaded TRH (TRH + MVF), unloaded TRH (TRH) or no material (control). Bone healing was evaluated 14 and 35 days postoperatively. MVF incorporated into TRH exhibited less apoptotic cells and showed a stable vessel morphology compared to controls. Micro-computed tomography revealed a reduced bone volume in TRH + MVF femurs. Histomorphometry showed less bone and more fibrous tissue after 35 days in TRH + MVF femurs compared to controls. Accordingly, TRH + MVF femurs exhibited a lower osseous bridging score and a reduced bending stiffness. Histology and Western blot analysis revealed an increased vascularization and CD31 expression, whereas vascular endothelial growth factor (VEGF) expression was reduced in TRH + MVF femurs. Furthermore, the callus of TRH + MVF femurs showed increased receptor activator of NF-κB ligand expression and higher numbers of osteoclasts. These findings indicate that TRH is an appropriate carrier system for MVF. Application of TRH + MVF increases the vascularization of bone defects. However, this impairs bone healing, most likely due to lower VEGF expression during the early course of bone healing. STATEMENT OF SIGNIFICANCE In the present study we analyzed for the first time the in vivo performance of a thermoresponsive hydrogel (TRH) as a delivery system for bioactive microvascular fragments (MVF). We found that TRH represents an appropriate carrier for MVF as vascularization units and maintains their viability. Application of MVF-loaded TRH impaired bone formation in an established murine model of bone healing, although vascularization was improved. This unexpected outcome was most likely due to a reduced VEGF expression in the early phase bone healing.