Biomechanical comparison of fatigue and load-bearing -performance of elastic stable intramedullary nailing

Purpose: Elastic stable intramedullary nailing (ESIN) is a very common method for the treatment of pediatric long bone fractures. Because of the fact that ESIN nails offer the chance of micromotion during the healing process, this method is beneficial in comparison to rigid bone fixation and stimulates the formation of a callus [1]. The time between the incident of the fracture and complete generation of the stabilizing callus seems to be a critical phase for the implants’ load-bearing. Torsional and axial stability has to be ensured by the ESIN implant during this phase. Methods: Because of the studies aim of monitoring the period until the formation of a callus, ovine cadaver -tibiae (3–4 months old) were implanted regarding clinical standards after osteotomy at the mid diaphyseal region. Four different combinations of locking systems and ESIN implants were observed during this study. Synthes TEN -Titanium with endcaps (n = 7), Hofer Medical HSNesin Titanium unlocked (n = 8), Hofer Medical STEN Steel with eye and 3-mm screw (n = 8), and Hofer Medical HSNesin Titanium with plug and 3mm screw (n = 8) were used. All nails were 3 mm in diameter. Cyclic mechanical loading was applied using a commercial uniaxial testing device (1710DLL-5KN, Dynamess, Germany), and a pneumatic torsion testing module which was constructed by one of the authors. This device is able to apply axial load and torque to the specimen simultaneously. Results: Juvenile ovine bones were used in this study to generate similar conditions as in pediatric long bones. All samples failed by a closure of the initial osteotomy gap of 10 mm. The results of biomechanical tests showed significantly higher load bearing capability with each interlocking system than with the unlocked ESIN. (1000 N max. compared with 200 N). The unlocked system and the endcap ESIN failed very abrupt, whereas the 3-mm plug and the steel system failed slowly. Above all, the 3-mm plug with steel ESIN experienced gap closure without any damage to plugs or screws, which led to a distal penetration of the diaphysis by the nails. Conclusions: Interlocking systems seem to be beneficial for stability of ESIN nailing under cyclic and simultaneous axial and torsional loading. The strongest combinations in this study were Hofer steel nails and Hofer plugs with 3-mm locking screws. Significance: Different combinations of ESIN nails and interlocking systems show diverse load bearing behaviors. Desirable characteristics of nonabrupt failure during the nails loading and maximal strength of interlocking systems could be established. REFERENCE [1] Bishop, N.E., van Rhijn, M., Tami, I., Corveleijn, R., Schneider, E., Ito, K. Shear does not necessarily inhibit bone healing. Clinical Orthopaedics and Related Research. 443

Median Nerve Palsy following Elastic Stable Intramedullary Nailing of a Monteggia Fracture: An Unusual Case and Review of the Literature

Monteggia fractures are rare in children, and subtle radial head dislocations, with minor plastic deformation of the ulna, may be missed in up to a third of cases. Complications of Monteggia fractures-dislocations include persistent radial head dislocation, forearm deformity, elbow stiffness, and nerve palsies at the time of presentation. An unusual case of median nerve palsy following elastic stable intramedullary nailing of a type I Monteggia lesion in a 6-year-old girl is presented, and we highlight that, although most nerve palsies associated with a Monteggia fracture-dislocations are treated expectantly in children, early intervention here probably provided the best outcome

Animal Models in Orthopedic Research: The Proper Animal Model to Answer Fundamental Questions on Bone Healing Depending on Pathology and Implant Material

Different species vary in bone metabolism, especially in modeling and remodeling of the bone. Human-related diseases with severe outcomes on bone, such as osteoporosis or osteoarthritis, are often reflected in animal models, which cannot adequately mimic the human situation. The pre-clinical investigation of implant materials in vivo complicates the search for the ideal animal model, especially when combining pathologic bone diseases and implant material. For instance, while alterations in trabecular bone architecture are investigated in female osteoporotic rats, rodents commonly lack cortical bone remodeling or secondary osteon formation. Small ruminants are commonly used to study long bone defects or orthopedic materials, due to their comparability to humans regarding body weight, bone size, and fracture healing. Nevertheless, there are important differences between human and ruminant models: plexiform cortical bone, seasonal bone loss, and stronger trabecular bone appear in sheep compared to humans. This chapter will summarize fundamental differences in bone quality between different animal models used for orthopedic and implant material research. Thus, choosing the ideal animal model to answer the proposed research question remains the key to guarantee a solid and excellent scientific study

3D nanoscale analysis of bone healing around degrading Mg implants evaluated by X-ray scattering tensor tomography

The nanostructural adaptation of bone is crucial for its biocompatibility with orthopedic implants. The bone nanostructure also determines its mechanical properties and performance. However, the bone\u27s temporal and spatial nanoadaptation around degrading implants remains largely unknown. Here, we present insights into this important bone adaptation by applying scanning electron microscopy, elemental analysis, and small-angle X-ray scattering tensor tomography (SASTT). We extend the novel SASTT reconstruction method and provide a 3D scattering reciprocal space map per voxel of the sample\u27s volume. From this reconstruction, parameters such as the thickness of the bone mineral particles are quantified, which provide additional information on nanostructural adaptation of bone during healing. We selected a rat femoral bone and a degrading ZX10 magnesium implant as model system, and investigated it over the course of 18 months, using a sham as control. We observe that the bone\u27s nanostructural adaptation starts with an initially fast interfacial bone growth close to the implant, which spreads by a re-orientation of the nanostructure in the bone volume around the implant, and is consolidated in the later degradation stages. These observations reveal the complex bulk bone-implant interactions and enable future research on the related biomechanical bone responses. Statement of significance: Traumatic bone injuries are among the most frequent causes of surgical treatment, and often require the placement of an implant. The ideal implant supports and induces bone formation, while being mechanically and chemically adapted to the bone structure, ensuring a gradual load transfer. While magnesium implants fulfill these requirements, the nanostructural changes during bone healing and implant degradation remain not completely elucidated. Here, we unveil these processes in rat femoral bones with ZX10 magnesium implants and show different stages of bone healing in such a model system

The effects of physical activity (treadmill and vibration stimulation training) on RANKL and OPG expression in bone cells, in rats with glucorticoid-induced osteoporosis

The aim of this study was to investigate bone tissue and plasma levels of RANKL and OPG in rats with prednisolone-induced osteoporosis and to evaluate the outcomes of physical activity on the skeletal system by treadmill and vibration platform training. Osteoporosis is a disease characterised by low bone mass and structural deterioration of bone tissue leading to bone fragility. Vibration exercise is a new and effective measure to prevent muscular atrophy and osteoporosis. The animals were divided into 5 groups. 1: control rats; 2: rats with osteoporosis receiving prednisolone; 3: rats receiving prednisolone and treadmill training; 4: rats receiving prednisolone and vibration stimulation training; 5: rats receiving prednisolone, treadmill training and vibration stimulation training. Bone evaluations used whole-body scans, histology and histomorphometric analysis. RANKL and OPG expression was evaluated by immunohistochemistry and biochemical analysis. After treatment, our data demonstrated that RANKL expression was significantly increased in groups 2 and 3 and decreased in groups 4 and 5. Conversely, OPG expression was significantly decreased in groups 2 and 3 and increased in groups 4 and 5. In conclusion, our findings suggest that mechanical stimulation inhibits the activity of RANKL. This finding provides new insights into the occurrence and progression of osteoporosis

The effects of physical activity (treadmill and vibration stimulation training) on Caspase-3 and Lubricin expression in articular cartilage in rats with glucorticoid-induced osteoarthritis

Glucocorticoids are considered the most powerful anti-inflammatory and immunomodulating drugs. However a number of side effects is well documented in different diseases, also in the articular cartilage where increase or decrease the synthesis of extracellular matrix components hormone dependent. 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 osteoarthritis and to evaluate the outcomes of physical activity on the articular cartilage by treadmill and vibration platform training. The animals were divided into 5 groups, bone and cartilage evaluations used 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 normal equipared to control group. Our findings suggest that it might be possible that the mechanical stimulation in the articular cartilage could release lubricin antibody that are capable of inhibiting caspase-3 activity preventing chondrocytes death. We can assume that the physiological balance between lubricin and caspase-3 could mantein the integrity of cartilage. So in certain diseases such as osteoporosis, mechanical stimulation could be a possible therapeutic treatment. With our results we can venture the hypothesis that a mild physical activity could also be used as a therapeutic treatment for cartilage disease such as osteoarthritis

A likelihood ratio approach for utilizing case-control data in the clinical classification of rare sequence variants:Application to BRCA1 and BRCA2

A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.</p

Common variants in breast cancer risk loci predispose to distinct tumor subtypes.

BACKGROUND: Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. METHODS: Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. RESULTS: Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. CONCLUSION: This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction