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INTRODUCTION: Glucocorticoids are essential in the treatment of many chronic inflammatory and malignant diseases but are known to have detrimental effects on bone. This study aimed to investigate the effects of prednisone on osteoclast functioning in vivo in the calvaria particle-induced bone loss mouse model. METHODS: 12-week-old male C57BL6/J mice received subcutaneously implanted prednisone (2.5 mg/d, 60 day release (n = 14)) or placebo pellets (n = 10). Osteolysis of the calvaria bone was induced two weeks later by application of ultra-high-molecular-weight polyethylene- (UHMWPE) particles to the dome (vs sham operation). The extent of osteolysis was determined histologically and by micro-computer tomography. RESULTS: Prednisone significantly inhibited particle-induced osteolysis in the skull. No significant difference in osteoclast numbers was seen in mice with prednisone vs placebo treatment. Prednisone treatment alone without particle application did not reduce bone mineral density or deterioration in bone microarchitecture parameters. CONCLUSIONS: The calvaria particle-induced bone loss mouse model can be adapted to investigate osteoclast activity in vivo and the effect of prednisone on osteoclasts. In this preventive experimental design, the application of short-term low-dose prednisone has osteoprotective effects without measurable systemic side effects on bone parameters.
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INTRODUCTION: Underwater rugby (UWR) is a team sport which combines swimming sprints, apnoea diving, a good overview of the three-dimensional underwater space and wrestling for the ball.This was the first epidemiological study of UWR injuries in a large international collective. METHODS: A questionnaire containing 124 questions was distributed to 198 active UWR players and completed under the supervision of medical staff. Demographic data and information about injuries in ten different body regions were collected. RESULTS: Of the 198 respondents, 106 (53.5%) were male and 92 (46.5%) were female. On average, each UWR player suffered a median of 19.5 (IQR 44) injuries. Based on the exposure time, means of 37.7 (SD 90.0) injuries per 1000 playing hours per player and 9.9 (20.1) injuries per year were found. Significant injuries mainly occurred to the head region (45.7%). Bruises and sprains were observed more often than fractures and dislocations. Male athletes had a longer total injury break time (median 4.8 [IQR 10.5] days), than female athletes (4 [8.6] days). Female athletes had more injuries (median 20 [IQR 26.8]) than male athletes (18.5 [63]). The length of the injury-related break time increased with the rise in body mass index. CONCLUSIONS: The risk of severe injury in UWR is low compared to other ball sports like water polo and rugby. UWR is played under water and the impact of tackles is lessened by the water. Further studies should record chronic injuries in UWR and establish measures to prevent injury.
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Traumatismos en Atletas , Fútbol Americano , Traumatismos en Atletas/epidemiología , Estudios Transversales , Femenino , Humanos , Incidencia , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: Various injuries in kitesurfing (KS) have been reported so far. The aim of this study was to validate the effect of different kite designs and safety equipment on the injury rate compared to older studies. METHODS: A retrospective epidemiological study based on an anonymous face-to-face survey was conducted amongst active kitesurfers. The questionnaire consisted of 66 questions focusing on the equipment used, injury rates, overuse injuries and gender differences. A stepwise Poisson-Model was used to identify injury-associated factors. RESULTS: A total of 202 kitesurfers with a mean age of 31.8±9.1 years and 698.2±931.5 hours of KS experience were included. 2613 injuries were recorded (18.5/1000 hours KS). Almost 50% were hematomas, bruises or cuts. 3.9% of all injuries (0.71/1000 hours KS) were time-loss injuries of more than one week. Female kitesurfers had a significantly greater injury rate, were less experienced and fewer of them used C-kites. Height, weight, primary kite spot, experience, physical activity, warm-up/stretching, the type of kite and control bar used, and the use of a board leash were independent factors associated to injury rate. The lower extremity, the elbow, thorax and abdomen were at risk for overuse injuries. CONCLUSIONS: An influence of equipment on injuries could be statistically shown. The overall injury rate in KS did not decline in the last decades, but time-loss injuries did.
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Traumatismos en Atletas/etiología , Equipo Deportivo , Deportes Acuáticos/lesiones , Adulto , Contusiones/etiología , Trastornos de Traumas Acumulados/etiología , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores Sexuales , Ejercicio de Calentamiento , Adulto JovenRESUMEN
BACKGROUND: Aseptic loosening is a main cause for revision surgery after total hip arthroplasty (THA) and there is no reliable marker for the early detection of patients at high risk. This study has been performed to validate association of the T393C polymorphism (rs7121) in the GNAS1 gene, encoding for the alpha-subunit of heterotrimeric G-protein Gs, with risk for and time to aseptic loosening after THA, which has been demonstrated in our previous study. METHODS: 231 patients with primary THA and 234 patients suffering from aseptic loosening were genotyped for dependency on GNAS1 genotypes and analyzed. RESULTS: Genotyping revealed almost similar minor allele frequencies of 0.49 and 0.46, respectively. Consistently, genotype distributions of both groups were not significantly different (p = 0.572). Neither gender nor GNAS1 genotype showed a statistically significant association with time to loosening (p = 0.501 and p = 0.840). Stratification by gender, as performed in our previous study, was not able to show a significant genotype-dependent difference in time (female p = 0.313; male p = 0.584) as well as median time to aseptic loosening (female p = 0.353; male p = 0.868). CONCLUSION: This study was not able to confirm the results of our preliminary study. An association of the GNAS1 T393C polymorphisms with risk for and time to aseptic loosening after THA is unlikely.
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Artroplastia de Reemplazo de Cadera/efectos adversos , Cromograninas/genética , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Polimorfismo de Nucleótido Simple , Complicaciones Posoperatorias/genética , Falla de Prótesis , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación MissenseRESUMEN
Aseptic loosening is a major cause of revision surgery of total hip arthroplasty (THA). Only few host factors affecting aseptic loosening have been identified until now, although they are urgently needed to identify and possibly treat those patients at higher risk for aseptic loosening. To determine whether the functional single nucleotide polymorphism (SNP) c.-938C>A (rs2279115), located in the promoter region of the BCL2 gene has an impact on aseptic loosening of THA we genotyped and analyzed 234 patients suffering from aseptic loosening and 231 patients after primary THA. The polymorphism is associated with risk for aseptic loosening with the CC genotype at highest risk for aseptic loosening, Odds Ratio CC vs. AA 1.93, 95%CI 1.15-3.25, p = 0.013. In contrast, low risk AA genotype carriers that still developed aseptic loosening showed a significantly shorter time to aseptic loosening than patients carrying the C allele (p = 0.004). These results indicate that the BCL2 -938C>A polymorphism influences the occurrence and course of aseptic loosening and suggests this polymorphism as an interesting candidate for prospective studies and analyses in THA registers.
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Artroplastia de Reemplazo de Cadera/efectos adversos , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas , Falla de Prótesis , Proteínas Proto-Oncogénicas c-bcl-2/genética , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Factores de Riesgo , Factores de TiempoRESUMEN
An aging population with higher bone turnover intensifies the need for joint replacement surgery. However, particle-induced osteolysis (PIO) remains a major cause of early implant loosening. Differences in bone remodeling between young and aged Calcitonin (CT)- and α-CGRP (Calcitonin gene-related peptide)-deficient mice (Calca(-/-)) might modify our previous findings regarding CT/α-CGRP in PIO. This may have important implications for PIO in an aging population. Four groups of twelve-month-old wild-type and Calca(-/-) mice underwent either SHAM surgery with and without CT, or polyethylene-particle implantation with related treatment. Morphometric changes were detected using µ-CT, histomorphometric analysis and by counting TRAP(+) cells (osteoclast-staining). Bone remodeling was assessed using serum and urinary markers. There was no osteolysis in aged particle-treated Calca(-/-) animals and the effect of CT on PIO was reduced compared to wild-type mice. However, there were significantly higher numbers of TRAP(+) cells in Calca(-/-) animals, and bone remodeling markers revealed a significant increase in OPG/OCN and a significant reduction in RANKL compared to aged wild-type mice. CT/α-CGRP modulates bone cell activity in PIO in aged mice in a way that is distinct from young animals. This may have implications for the treatment of PIO in the periprosthetic surface of joint replacements in an aging population.
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Péptido Relacionado con Gen de Calcitonina/genética , Calcitonina/genética , Modelos Animales de Enfermedad , Osteólisis , Ligando RANK/fisiología , Animales , Remodelación Ósea , RatonesRESUMEN
INTRODUCTION: Severe bleeding after trauma frequently leads to a poor outcome. Prehospital fluid replacement therapy is regarded as an important primary treatment option. Our study aimed to assess the influence of prehospital fluid replacement therapy on the post-traumatic course of severely injured patients in a retrospective analysis of matched pairs. PATIENTS AND METHODS: The data of 51,425 patients of the Trauma Registry of the German Society for Trauma Surgery were analysed. The following patients were included: Injury Severity Score ≥ 16 points, primary admission, age ≥ 16 years, no isolated brain injury, transfusion of at least one unit of packed red blood cells (pRBC), systolic blood pressure ≥ 60 mmHg at the accident site. The patients were divided into two groups according to the following matched-pair criteria (low-volume: 0-1500 ml prehospital volume replaced; high-volume: ≥ 1501 ml prehospital volume): intubation at the accident site (yes/no), time from injury to hospital ± 10 min., means of rescue (emergency helicopter, MICU), Abbreviated Injury Scale (body regions), injury year, systolic blood pressure and age (years). All patients were managed by an emergency doctor at the accident site. RESULTS: A total of 948 patients in each group met the inclusion criteria. Increasing replacement volume was associated with an increased need for transfusion (pRBCs: low-volume: 7 units, high-volume: 8.3 units; p<0.001) and a reduced ability to coagulate (prothrombin ratio (PR): low-volume: 68%, high-volume: 61.5%; p<0.001). Patients in shock (systolic BP<90 mmHg) upon admission to the hospital were equally in both groups (25.6%; p=0.98). Significantly higher lethality was observed in cases of increasing volume (low-volume: 22.7%, high-volume: 27.6%; p<0.01). CONCLUSIONS: Excessive prehospital fluid replacement leads to an increased mortality rate. The results of this study support the concept of restrained volume replacement in the prehospital treatment of patients with severe trauma.
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Servicios Médicos de Urgencia , Fluidoterapia/efectos adversos , Traumatismo Múltiple/mortalidad , Resucitación/métodos , Heridas y Lesiones/mortalidad , Escala Resumida de Traumatismos , Adulto , Femenino , Fluidoterapia/métodos , Alemania/epidemiología , Escala de Coma de Glasgow , Humanos , Puntaje de Gravedad del Traumatismo , Intubación/métodos , Masculino , Análisis por Apareamiento , Traumatismo Múltiple/complicaciones , Traumatismo Múltiple/terapia , Sistema de Registros , Estudios Retrospectivos , Sepsis/mortalidad , Choque Hemorrágico/mortalidad , Factores de Tiempo , Heridas y Lesiones/complicaciones , Heridas y Lesiones/terapiaRESUMEN
BACKGROUND: Periprosthetic osteolysis is a major cause of aseptic loosening in joint arthroplasty. This study investigates the impact of CT (calcitonin) deficiency and CT substitution under in-vivo circumstances on particle-induced osteolysis in Calca -/- mice. METHODS: We used the murine calvarial osteolysis model based on ultra-high molecular weight polyethylene (UHMWPE) particles in 10 C57BL/6J wild-type (WT) mice and twenty Calca -/- mice. The mice were divided into six groups: WT without UHMWPE particles (Group 1), WT with UHMWPE particles (Group 2), Calca -/- mice without UHMWPE particles (Group 3), Calca -/- mice with UHMWPE particles (Group 4), Calca -/- mice without UHMWPE particles and calcitonin substitution (Group 5), and Calca -/- mice with UHMWPE particle implantation and calcitonin substitution (Group 6). Analytes were extracted from serum and urine. Bone resorption was measured by bone histomorphometry. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase (TRACP) + cells. RESULTS: Bone resorption was significantly increased in Calca -/- mice compared with their corresponding WT. The eroded surface in Calca -/- mice with particle implantation was reduced by 20.6% after CT substitution. Osteoclast numbers were significantly increased in Calca -/- mice after particle implantation. Serum OPG (osteoprotegerin) increased significantly after CT substitution. CONCLUSIONS: As anticipated, Calca -/- mice show extensive osteolysis compared with wild-type mice, and CT substitution reduces particle-induced osteolysis.
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Conservadores de la Densidad Ósea/farmacología , Calcitonina/deficiencia , Osteólisis/tratamiento farmacológico , Falla de Prótesis/efectos adversos , Animales , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/prevención & control , Calcitonina/genética , Calcitonina/fisiología , Recuento de Células , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microesferas , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteólisis/patología , Osteólisis/prevención & control , Osteoprotegerina/sangre , Polietileno/toxicidad , Cráneo/efectos de los fármacos , Cráneo/metabolismo , Cráneo/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Recent studies demonstrated an impact of the nervous system on particle-induced osteolysis, the major cause of aseptic loosening of joint replacements. METHODS: In this study of MG-63 osteoblast-like cells we analyzed the influence of ultra-high molecular weight polyethylene (UHMWPE) particles and the neurotransmitter alpha-calcitonin gene-related peptide (CGRP) on the osteoprotegerin/receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factorκB (OPG/RANKL/RANK) system. MG-63 cells were stimulated by different UHMWPE particle concentrations (1:100, 1:500) and different doses of alpha-CGRP (10-7 M, 10-9 M, 10-11 M). RANKL and OPG mRNA expression and protein levels were measured by RT-PCR and Western blot. RESULTS: Increasing particle concentrations caused an up-regulation of RANKL after 72 hours. Alpha-CGRP showed a dose-independent depressive effect on particle-induced expression of RANKL mRNA in both cell-particle ratios. RANKL gene transcripts were significantly (P < 0.05) decreased by alpha-CGRP treatment after 48 and 72 hours. OPG mRNA was significantly down-regulated in a cell-particle ratio of 1:500 after 72 hours. Alpha-CGRP concentrations of 10-7 M lead to an up-regulation of OPG protein. CONCLUSION: In conclusion, a possible osteoprotective influence of the neurotransmitter alpha-CGRP on particle stimulated osteoblast-like cells could be shown. Alpha-CGRP might be important for bone metabolism under conditions of particle-induced osteolysis.
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BACKGROUND AND PURPOSE: A linkage between the neurotransmitter alpha-calcitonin gene-related peptide (alpha-CGRP) and particle-induced osteolysis has been shown previously. The suggested osteoprotective influence of alpha-CGRP on the catabolic effects of ultra-high molecular weight polyethylene (UHMWPE) particles is analyzed in this study in primary human osteoblasts. METHODS: Primary human osteoblasts were stimulated by UHMWPE particles (cell/particle ratios 1:100 and 1:500) and different doses of alpha-CGRP (10(-7 )M, 10(-9 )M, 10(-11 )M). Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) mRNA expression and protein levels were measured by RT-PCR and Western blot. RESULTS: Particle stimulation leads to a significant dose-dependent increase of RANKL mRNA in both cell-particle ratios and a significant down-regulation of OPG mRNA in cell-particle concentrations of 1:500. A significant depression of alkaline phosphatase was found due to particle stimulation. Alpha-CGRP in all tested concentrations showed a significant depressive effect on the expression of RANKL mRNA in primary human osteoblasts under particle stimulation. Comparable reactions of RANKL protein levels due to particles and alpha-CGRP were found by Western blot analysis. In cell-particle ratios of 1:100 after 24 hours the osteoprotective influence of alpha-CGRP reversed the catabolic effects of particles on the RANKL expression. INTERPRETATION: The in-vivo use of alpha-CGRP, which leads to down-regulated RANKL in-vitro, might inhibit the catabolic effect of particles in conditions of particle induced osteolysis.
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Péptido Relacionado con Gen de Calcitonina/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Polietilenos/farmacología , Ligando RANK/metabolismo , Western Blotting , Células Cultivadas , Humanos , Persona de Mediana Edad , Ligando RANK/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: Micro-structural changes associated with ultra high molecular weight polyethylene particle (UHMWPE) induced osteolysis, the most frequent cause of aseptic loosening, have been intensively investigated in the mammalian calvarian model by histomorphometry and micro-computed tomography. However, little is known regarding the serological changes that occur during this process. METHODS: Serological parameters for bone metabolism [calcium, phosphate, osteocalcin (OCN), deoxypyridinoline (DPD)/creatinine, alkaline phosphatase, osteoprotegerin and receptor activator of nuclear factor-κB] were analyzed in this animal model for particle induced osteolysis. Ten C57BL/6 mice were divided at random into sham operated and UHM-WPE implanted groups. Blood and urine samples were collected prior to and at 14 days after surgery. RESULTS: Implantation of UHMWPE lead to a significant decrease in bone volume (p=0.027). Both groups (sham/UHMWPE) showed a significant increase in calcium (p=0.004/p=0.027) and phosphate (p=0.001/p=0.001), without correlation to particle implantation. Significantly higher concentrations of DPD/creatinine (p=0.034) and OCN (p=0.022) were found after implantation of UHM-WPE. In addition, parameters could not be correlated to particle induced osteolysis. CONCLUSIONS: DPD can be regarded as a valuable parameter for detecting UHMWPE induced osteolysis in the calvarian model. Further studies of serum parameters should focus on the clinical relevance in aseptic prosthetic loosening.