[Supracondylar humeral fractures in childhood]. / Suprakondyläre Humerusfraktur im Kindesalter.

The classification of supracondylar humeral fractures in German-speaking areas is carried out according to von Laer, which has been appropriated from the AO system and has the advantage that it can be used to derive the treatment. When indicated immediate surgery is given preference over a delayed treatment. The result is controlled by functional tests directly during the operation. Instability of the fracture and correct placement of the Kirschner (K) wires are challenging. Alternatives are an external fixator and elastically stable intramedullary nailing (ESIN). Concomitant injuries initially affect the median nerve and the brachial artery and secondarily the radial nerve. Lesions of the ulnar nerve are mostly a postoperative complication. The bony consolidation is achieved after 3-4 weeks and afterwards implant removal can be safely carried out. Embedded K­wires and ESIN are removed after 3-6 months, depending on the surgical capacity and complaints of the patient.

Assessment of pharmacokinetics for microvessel proliferation by DCE-MRI for early detection of physeal bone bridge formation in an animal model.

OBJECTIVES: Bone bridge formation occurs after physeal lesions and can lead to growth arrest if not reversed. Previous investigations on the underlying mechanisms of this formation used histological methods. Therefore, this study aimed to apply a minimally invasive method using dynamic contrast-enhanced MRI (DCE-MRI). MATERIALS AND METHODS: Changes in functional parameters related to the microvessel system were assessed in a longitudinal study of a cohort of an animal model applying a reference region model. The development of morphology of the injured physis was investigated with 3D high-resolution MRI. To acquire complementary information for MRI-related findings qRT-PCR and immunohistochemical data were acquired for a second cohort of the animal model. RESULTS: The evaluation of the pharmacokinetic parameters showed a first rise of the transfer coefficient 7 days post-lesion and a maximum 42 days after operation. The analysis of the complementary data showed a connection of the first rise to microvessel proliferation while the maximum value was linked to bone remodeling. CONCLUSION: The pharmacokinetic analysis of DCE-MRI provides information on a proliferation of microvessels during the healing process as a sign for bone bridge formation. Thereby, DCE-MRI could identify details, which up to now required analyses of highly invasive methods.

Differential apoptotic response of MC3T3-E1 pre-osteoblasts to biodegradable magnesium alloys in an in vitro direct culture model.

The biodegradable magnesium-based implants have been widely utilized in medical orthopedic applications in recent years. We have recently shown that direct culture on Pure Mg and Mg2Ag alloys lead to a progressive differentiation impairment of MC3T3-E1 pre-osteoblasts. In this study, we aimed to analyze the apoptotic reaction of MC3T3-E1 cells in response to the direct culture on Pure Mg, Mg2Ag and Extreme High Pure Mg (XHP Mg) alloy samples. Our results demonstrated that long-term culturing of MC3T3-E1 cells on Pure Mg and Mg2Ag alloys induce time-dependent expression of active caspase-3 (active casp-3) and cleaved PARP-1 (cl. PARP-1), the hallmark of apoptosis reactions concomitant with a significant increase in the number of dead cells. However, direct culture on XHP Mg material results in a lower number of dead cells in comparison to Pure Mg and Mg2Ag alloys. Furthermore, XHP Mg materials influence expression of apoptotic markers in a process resembles that of observed in osteogenic condition apparently indicative of MC3T3-E1 osteodifferentiation. This study indicates that Mg alloy samples mediated differential apoptotic reactions of MC3T3-E1 cells can be ascribed to factors such as distinct topography and hydrophobicity features of Mg material surfaces, contrasting nature/composition of corrosion products as well as different impurities of these materials. Therefore, initial Mg alloys surface preparation, controlling the growth and composition of corrosion products and Mg alloys purity enhancement are necessary steps towards optimizing the Mg alloys usage in medical orthopedic applications.

Using a worst pain intensity measure in children and adolescents.

AIMS: To explore inconsistencies and the reliability in worst pain intensity ratings in children. BACKGROUND: Asking for worst pain always requires a retrospective evaluation which is controversially discussed. DESIGN: Retrospective analysis of registry data and a prospective study. METHODS: Retrospective study: 5970 patients [age: 10·2(4·0) years, female: 41% data collection: 2008-2015]; Prospective study: 240 patients [age: 14·7(1·9) years, female: 43%, data collection 2013-2014] were included. In both studies, the number of implausible pain intensity ratings was calculated (both studies: worst pain lower than movement pain or pain at rest, prospective study: number of patients reporting lower pain intensity ratings in worst pain items for the same time period in a second assessment). Test-retest reliability was calculated for the prospective study. Changes in worst pain ratings were analyzed using Wilcoxon signed ranks test. RESULTS: Test-retest reliability ranged from ρ = 0·77-0·90. In the retrospective study, 8·9% (95%CI: 8·2-9·6%) of our patients reported higher movement and/or pain at rest compared with worst pain. In the prospective study, 35·8% (95%CI: 30·0-42·1%) reported higher activity pain ratings compared with worst pain ratings in at least one pain assessment; 13·8% of the pediatric patients reported lower pain intensity ratings in worst pain items in a second assessment compared with the first assessment. CONCLUSION: Nine to 36% of our patients showed inconsistent worst pain ratings. To overcome this problem, more specific pain intensity items, more than one item or a better instruction for pediatric patients could be used.

The origin points of the knee collateral ligaments: an MRI study on paediatric patients during growth.

PURPOSE: Different femoral origins for both the medial collateral ligament (MCL) and the lateral collateral ligament (LCL) have been reported in the growing skeleton (epiphyseal and metaphyseal). Knowledge about the exact attachment sites is mandatory for anatomically correct reconstruction. This study assesses the femoral origins of the knee collateral ligaments in skeletally immature individuals using magnetic resonance imaging (MRI). METHODS: MRIs of 336 knee joints (median age 15 years (range 2-18 years), m = 209 and f = 127) were retrospectively analysed to assess the distances between the femoral origins of the MCL and LCL to the distal femoral growth plate. In 175 patients, the body sizes were additionally retrieved from medical records. RESULTS: Both MCL and LCL ligament origins were invariably located on the epiphysis. Mean MCL origin-growth plate distance was 9.6 mm (SD 2.1 mm; range 2.2-13.6 mm) in boys and 8.6 mm (SD 1.5 mm; range 3.4-12.0 mm) in girls. Mean LCL origin-growth plate distance was 9.3 mm (SD 1.8 mm; range 4.3-13.0 mm) in boys and 8.2 mm (SD 1.5 mm; range 3.4-11.8 mm) in girls. The distance between the growth plate and both collateral ligaments as well as the length of the LCL correlated positively with patients' age and body size (MCL R(2) = 0.673 and 0.556, LCL R (2) = 0.734 and 0.645, LCL length R(2) = 0.589 and 0.741; all p < 0.001). CONCLUSIONS: During growth, the femoral origins of the MCL and the LCL are constantly located on the distal femoral epiphysis. There is a linear increase in the distances from the ligaments' origins to the growth plate according to age and body size. This new information may be of clinical importance for reconstructive surgery of the knee's collateral ligaments.

Biomarkers of Chondrocyte Apoptosis and Autophagy in Osteoarthritis.

Cell death with morphological and molecular features of apoptosis has been detected in osteoarthritic (OA) cartilage, which suggests a key role for chondrocyte death/survival in the pathogenesis of OA. Identification of biomarkers of chondrocyte apoptosis may facilitate the development of novel therapies that may eliminate the cause or, at least, slow down the degenerative processes in OA. The aim of this review was to explore the molecular markers and signals that induce chondrocyte apoptosis in OA. A literature search was conducted in PubMed, Scopus, Web of Science and Google Scholar using the keywords chondrocyte death, apoptosis, osteoarthritis, autophagy and biomarker. Several molecules considered to be markers of chondrocyte apoptosis will be discussed in this brief review. Molecular markers and signalling pathways associated with chondroycte apoptosis may turn out to be therapeutic targets in OA and approaches aimed at neutralizing apoptosis-inducing molecules may at least delay the progression of cartilage degeneration in OA.

Cellular reactions to biodegradable magnesium alloys on human growth plate chondrocytes and osteoblasts.

PURPOSE: In recent decades operative fracture treatment using elastic stable intramedullary nails (ESINs) has mainly taken precedence over conservative alternatives in children. The development of biodegradable materials that could be used for ESINs would be a further step towards treatment improvement. Due to its mechanical and elastic properties, magnesium seems to be an ideal material for biodegradable implant application. The aim of this study was therefore to investigate the cellular reaction to biodegradable magnesium implants in vitro. METHODS: Primary human growth plate chondrocytes and MG63 osteoblasts were used for this study. Viability and metabolic activity in response to the eluate of a rapidly and a slower degrading magnesium alloy were investigated. Furthermore, changes in gene expression were assessed and live cell imaging was performed. RESULTS: A superior performance of the slower degrading WZ21 alloy's eluate was detected regarding cell viability and metabolic activity, cell proliferation and morphology. However, the ZX50 alloy's eluate induced a favourable up-regulation of osteogenic markers in MG63 osteoblasts. CONCLUSIONS: This study showed that magnesium alloys for use in biodegradable implant application are well tolerated in both osteoblasts and growth plate chondrocytes respectively.

Ex vivo organotypic bone slice culture reveals preferential chondrogenesis after sustained growth plate injury.

Postnatal bone growth primarily relies on chondrocyte proliferation and osteogenic differentiation within the growth plate (GP) via endochondral ossification. Despite its importance, the GP is vulnerable to injuries, affecting 15-30 % of bone fractures. These injuries may lead to growth discrepancies, influence bone length and shape, and negatively affecting the patient's quality of life. This study aimed to investigate the molecular and cellular physiological and pathophysiological regeneration following sustained growth plate injury (GPI) in an ex vivo rat femur organotypic culture (OTC) model. Specifically, focusing on postnatal endochondral ossification process. 300 µm thick ex vivo bone cultures with a 2 mm long horizontal GPI was utilized. After 15 days of cultivation, gene expression analysis, histological and immunohistochemistry staining's were conducted to analyze key markers of endochondral ossification. In our OTCs we observed a significant increase in Sox9 expression due to GPI at day 15. The Ihh-PTHrP feedback loop was affected, favoring chondrocyte proliferation and maturation. Ihh levels increased significantly on day 7 and day 15, while PTHrP was downregulated on day 7. GPI had no impact on osteoclast number and activity, but gene expression analysis indicated OTCs' efforts to inhibit osteoclast differentiation and activation, thereby reducing bone resorption. In conclusion, our study provides novel insights into the molecular and cellular mechanisms underlying postnatal bone growth and regeneration following growth plate injury (GPI). We demonstrate that chondrocyte proliferation and differentiation play pivotal roles in the regeneration process, with the Ihh-PTHrP feedback loop modulating these processes. Importantly, our ex vivo rat femur organotypic culture model allows for the detailed investigation of these processes, providing a valuable tool for future research in the field of skeletal biology and regenerative medicine.

Towards a better understanding of bone bridge formation in the growth plate - an immunohistochemical approach.

The growth plate at the end of long bones is the cartilaginous organ responsible for longitudinal bone growth in children. Trauma to the growth plate, i.e. fractures, can severely impair longitudinal bone growth, leading to growth disorders due to destruction of the epiphyseal circulation and formation of a bone bridge. From the clinical experience it is known that in some patients this bone bridge eventually disappears during the growth process. However, the molecular mechanisms involved in bone bridge formation and dissolution have not been clarified yet. The aim of this study was to investigate the spatial and temporal protein level of molecules potentially involved in these processes, i.e. RANKL, OPG, DKK-1, Coll 10, BMP-2 and IL-6, in an experimental rat model using an immunohistochemical approach. The results from our study suggest that bone bridge formation might be an early event starting immediately after growth plate injury and involving several pro-osteoblastic molecules, i.e. IL-6, BMP-2 as well as OPG and Coll X. In the late studied time points 3- and 9-month post-injury expression of anti-osteoblastic proteins, i.e. DKK1 and RANKL, was increased. This indicates that bone bridge dissolution might be a late event and potentially linked to Wnt signaling inhibition and RANK/RANKL signaling activation.

The effects of physical activity on apoptosis and lubricin expression in articular cartilage in rats with glucocorticoid-induced osteoporosis.

Glucocorticoids are considered the most powerful anti-inflammatory and immunomodulating drugs. However, a number of side-effects are well documented in different diseases, including articular cartilage, where increases or decreases in the synthesis of hormone-dependent extracellular matrix components are seen. The objective of this study has been to test the effects of procedures or drugs affecting bone metabolism on articular cartilage in rats with prednisolone-induced osteoporosis and to evaluate the outcomes of physical activity with treadmill and vibration platform training on articular cartilage. The animals were divided into 5 groups, and bone and cartilage evaluations were performed using whole-body scans and histomorphometric analysis. Lubricin and caspase-3 expression were evaluated by immunohistochemistry, Western blot analysis and biochemical analysis. These results confirm the beneficial effect of physical activity on the articular cartilage. The effects of drug therapy with glucocorticoids decrease the expression of lubricin and increase the expression of caspase-3 in the rats, while after physical activity the values return to normal compared to the control group. Our findings suggest that it might be possible that mechanical stimulation in the articular cartilage could induce the expression of lubricin, which is capable of inhibiting caspase-3 activity, preventing chondrocyte death. We can assume that the physiologic balance between lubricin and caspase-3 could maintain the integrity of cartilage. Therefore, in certain diseases such as osteoporosis, mechanical stimulation could be a possible therapeutic treatment. With our results we can propose the hypothesis that physical activity could also be used as a therapeutic treatment for cartilage disease such as osteoarthritis.

Post-traumatic caspase-3 expression in the adjacent areas of growth plate injury site: a morphological study.

The epiphyseal plate is a hyaline cartilage plate that sits between the diaphysis and the epiphysis. The objective of this study was to determine the impact of an injury in the growth plate chondrocytes through the study of histological morphology, immunohistochemistry, histomorphometry and Western Blot analyses of the caspase-3 and cleaved PARP-1, and levels of the inflammatory cytokines, Interleukin-6 (IL-6) and Tumor Necrosis Factor alpha (TNF-α), in order to acquire more information about post-injury reactions of physeal cell turnover. In our results, morphological analysis showed that in experimental bones, neo-formed bone trabeculae-resulting from bone formation repair-invaded the growth plate and reached the metaphyseal bone tissue (bone bridge), and this could result in some growth arrest. We demonstrated, by ELISA, increased expression levels of the inflammatory cytokines IL-6 and TNF-α. Immunohistochemistry, histomorphometry and Western Blot analyses of the caspase-3 and cleaved PARP-1 showed that the physeal apoptosis rate of the experimental bones was significantly higher than that of the control ones. In conclusion, we could assume that the inflammation process causes stress to chondrocytes that will die as a biological defense mechanism, and will also increase the survival of new chondrocytes for maintaining cell homeostasis. Nevertheless, the exact stimulus leading to the increased apoptosis rate, observed after injury, needs additional research to understand the possible contribution of chondrocyte apoptosis to growth disturbance.

Fracture of the ulnar styloid process negatively influences the outcome of paediatric fractures of the distal radius.

In paediatric patients with fractures of the distal radius, the consequences of associated ulnar styloid fractures are often underestimated. These may include persisting pain or functional deficits. The aim of the present study was to report the outcome of these fractures using a modified DASH-Score. All children with distal radius fractures treated in a two years period were analysed; only patients with a concomitant fracture of the ulnar styloid were included in the study.In addition, children with a non-union of the styloid at cast removal were asked to complete a postal questionnaire; the data were compared to those in a group of patients with isolated distal radius fractures. Patients reporting problems and those with a modified DASH score over 0.5 were invited for a long-term follow-up clinical and radiological examination. A concomitant fracture of the ulnar styloid was present in 11% of all distal radius fractures. At the time of cast removal 46 patients (89%) showed a delayed union of the ulnar styloid. The modified DASH Score of these patients at an average of 31 months (range: 24-40 months) was significantly worse (3.8; range: 0-24.2) compared to 0.7 (range 0-27.7) in the patients with isolated radius fractures after a mean of 27 months (range: 21-42 months). At follow-up, 7 patients showed a non-union of the ulnar styloid. Fractures of the base of the styloid process were more likely to develop non-union compared to fractures of its tip. The presence of an ulnar styloid fracture negatively influences the outcome of distal radius fractures. Patients with lesions of the ulnar styloid should be followed until union is observed and/or they are asymptomatic.

Fractures of the pelvis in children: a review of the literature.

Trauma is the leading cause of death in children. Pelvic ring injuries account for 0.3-4% of all paediatric injuries. The pattern of fractures differs to that seen in adults as it is more ductile. Pelvic ring injuries tend to be more stable as the relatively thick periosteum restricts bony displacement. Intrapelvic viscera are not well protected and can sustain injury in the absence of pelvic fractures. These injuries have traditionally been treated non-operatively. In this paper, we comprehensively review the literature and propose a protocol for treatment taking into consideration associated organ injuries, hemodynamic status of the patient, patient's age, type of fracture and the stability of the pelvic ring.

Newly Developed Resorbable Magnesium Biomaterials for Orbital Floor Reconstruction in Caprine and Ovine Animal Models-A Prototype Design and Proof-of-Principle Study.

BACKGROUND: orbital floor fractures have not been reconstructed using magnesium biomaterials. METHODS: To test technical feasibility, ex vivo caprine and ovine heads (n = 5) were used. Head tissues were harvested from pubescent animals (n = 5; mean age: 3.2 years; mean mass: 26.3 kg) and stored below 11 degrees for 7-10 days. All procedures were performed in a university animal resource facility. Two experienced maxillofacial surgeons performed orbital floor procedures in both orbits of all animals in a step-by-step preplanned dissection. A transconjunctival approach was chosen to repair the orbital floor with three different implants (i.e., magnesium implants; titanium mesh; and polydioxanone or PDO sheets). The position of each implant was evaluated by Cone-beam computed tomography (CBCT). RESULTS: Axial, coronal, and sagittal plane images showed good positioning of the magnesium plates. The magnesium plates had a radiographic visibility similar to that of the PDO sheets but lower than that of the titanium mesh. CONCLUSIONS: The prototype design study showed a novel indication for magnesium biomaterials. Further testing of this new biomaterial may lead to the first resorbable biomaterial with good mechanical properties for extensive orbital wall defects.

Disruption of Endochondral Ossification and Extracellular Matrix Maturation in an Ex Vivo Rat Femur Organotypic Slice Model Due to Growth Plate Injury.

Postnatal bone fractures of the growth plate (GP) are often associated with regenerative complications such as growth impairment. In order to understand the underlying processes of trauma-associated growth impairment within postnatal bone, an ex vivo rat femur slice model was developed. To achieve this, a 2 mm horizontal cut was made through the GP of rat femur prior to the organotypic culture being cultivated for 15 days in vitro. Histological analysis showed disrupted endochondral ossification, including disordered architecture, increased chondrocyte metabolic activity, and a loss of hypertrophic zone throughout the distal femur. Furthermore, altered expression patterns of Col2α1, Acan, and ColX, and increased chondrocyte metabolic activity in the TZ and MZ at day 7 and day 15 postinjury were observed. STEM revealed the presence of stem cells, fibroblasts, and chondrocytes within the injury site at day 7. In summary, the findings of this study suggest that the ex vivo organotypic GP injury model could be a valuable tool for investigating the underlying mechanisms of GP regeneration post-trauma, as well as other tissue engineering and disease studies.

Does early post-operative exercise influence bone healing kinetics? Preclinical evaluation of non-critical sized femur defect healing.

Physical exercise is a well-known modality for maintaining healthy locomotor mechanism. A detailed preclinical research on physical exercise effect on bone healing kinetics could help to improve the rehabilitation process after fracture treatment and bone remodeling. Our aim was to evaluate the effect of early post-operative exercise effect on bone microstructural changes in a rat model. Twenty Sprague Dawley male rats underwent bi-cortical 1.6 mm hole drilling in both femur diaphysis, after which (n = 10) underwent continuous treadmill training (TR) over two weeks, while the other group of rats (n = 10) was assigned to non-training (NT) control group. New bone formation labeling was performed by subcutaneous fluorochrome injections at day 5, 14 and 31. In vivo micro-computed tomography (µCT) scans were performed once a week during the 6-week post-operative period. Ten animals (five from each group) were euthanized at 3rd week while remaining animals were euthanized at 6th week. Femur samples were extracted and underwent ex vivo µCT and histological evaluation, while serum was used for evaluating alkaline phosphatase (ALP). µCT data demonstrated increased volume and surface of newly formed bone in defect area of TR group. Bone volume/Tissue volume (BV/TV) ratio and number of osteocytes showed an increase in TR group after 3-week period. Fluorochrome distances were increased between day 5 and 14 within the training group. Serum ALP level increased in both groups over 3- and 6-weeks. Post-operative exercise increases the bone healing kinetics and stimulates the new bone formation during and after the training protocol has ended.

The combined effect of zinc and calcium on the biodegradation of ultrahigh-purity magnesium implants.

Magnesium (Mg)-based implants are promising candidates for orthopedic interventions, because of their biocompatibility, good mechanical features, and ability to degrade completely in the body, eliminating the need for an additional removal surgery. In the present study, we synthesized and investigated two Mg-based materials, ultrahigh-purity ZX00 (Mg-Zn-Ca; <0.5 wt% Zn and <0.5 wt% Ca, in wt%; Fe-content <1 ppm) and ultrahigh-purity Mg (XHP-Mg, >99.999 wt% Mg; Fe-content <1 ppm), in vitro and in vivo in juvenile healthy rats to clarify the effect of the alloying elements Zn and Ca on mechanical properties, microstructure, cytocompatibility and degradation rate. Potential differences in bone formation and bone in-growth were also assessed and compared with state-of-the-art non-degradable titanium (Ti)-implanted, sham-operated, and control (non-intervention) groups, using micro-computed tomography, histology and scanning electron microscopy. At 6 and 24 weeks after implantation, serum alkaline phosphatase (ALP), calcium (Ca), and Mg level were measured and bone marrow stromal cells (BMSCs) were isolated for real-time PCR analysis. Results show that ZX00 implants have smaller grain size and superior mechanical properties than XHP-Mg, and that both reveal good biocompatibility in cytocompatibilty tests. ZX00 homogenously degraded with an increased gas accumulation 12 and 24 weeks after implantation, whereas XHP-Mg exhibited higher gas accumulation already at 2 weeks. Serum ALP, Ca, and Mg levels were comparable among all groups and both Mg-based implants led to similar relative expression levels of Alp, Runx2, and Bmp-2 genes at weeks 6 and 24. Histologically, Mg-based implants are superior for new bone tissue formation and bone in-growth compared to Ti implants. Furthermore, by tracking the sequence of multicolor fluorochrome labels, we observed higher mineral apposition rate at week 2 in both Mg-based implants compared to the control groups. Our findings suggest that (i) ZX00 and XHP-Mg support bone formation and remodeling, (ii) both Mg-based implants are superior to Ti implants in terms of new bone tissue formation and osseointegration, and (iii) ZX00 is more favorable due to its lower degradation rate and moderate gas accumulation.

Degradation behavior and osseointegration of Mg-Zn-Ca screws in different bone regions of growing sheep: a pilot study.

Magnesium (Mg)-based implants are highly attractive for the orthopedic field and may replace titanium (Ti) as support for fracture healing. To determine the implant-bone interaction in different bony regions, we implanted Mg-based alloy ZX00 (Mg < 0.5 Zn < 0.5 Ca, in wt%) and Ti-screws into the distal epiphysis and distal metaphysis of sheep tibiae. The implant degradation and osseointegration were assessed in vivo and ex vivo after 4, 6 and 12 weeks, using a combination of clinical computed tomography, medium-resolution micro computed tomography (µCT) and high-resolution synchrotron radiation µCT (SRµCT). Implant volume loss, gas formation and bone growth were evaluated for both implantation sites and each bone region independently. Additionally, histological analysis of bone growth was performed on embedded hard-tissue samples. We demonstrate that in all cases, the degradation rate of ZX00-implants ranges between 0.23 and 0.75 mm/year. The highest degradation rates were found in the epiphysis. Bone-to-implant contact varied between the time points and bone types for both materials. Mostly, bone-volume-to-total-volume was higher around Ti-implants. However, we found an increased cortical thickness around the ZX00-screws when compared with the Ti-screws. Our results showed the suitability of ZX00-screws for implantation into the distal meta- and epiphysis.