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1.
Arch Orthop Trauma Surg ; 130(4): 441-5, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19513735

RESUMEN

INTRODUCTION: Plain radiography, bone scintigraphy, digital subtraction arthrography and various other techniques can be used to evaluate loosening of hip replacements. These methods are associated with radiation exposure and some of them have an increased morbidity. Furthermore, in some cases the results are not conclusive. METHOD: The osteoclast biomarkers tartrate-resistant acid phosphatase 5b (TRAP 5b) and C-terminal telopeptides of type I collagen (CTX) in serum taken from 12 patients with aseptic loosening were measured. Serum samples from 24 other patients, 12 with an intact arthroplasty and 12 without any kind of joint replacement, served as control groups. RESULTS: The serum level of CTX was increased in comparison to the control groups, but the differences were not significant. In contrast, the increase in TRAP 5b in patients with aseptic loosening was highly significant (P < 0.001). A TRAP 5b value of 3.365 U/L was determined as a cut-off value, giving a sensitivity of 83.3% and specificity of 91.7% to differentiate the patients with aseptic loosening from those with an intact arthroplasty. Measurement of serum TRAP 5b may be a clinically relevant assay for monitoring patients after arthroplasty.


Asunto(s)
Fosfatasa Ácida/sangre , Artroplastia de Reemplazo de Cadera/efectos adversos , Prótesis de Cadera/efectos adversos , Isoenzimas/sangre , Fragmentos de Péptidos/sangre , Procolágeno/sangre , Falla de Prótesis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Colágeno Tipo I , Femenino , Humanos , Masculino , Persona de Mediana Edad , Péptidos , Fosfatasa Ácida Tartratorresistente
2.
J Biomed Mater Res A ; 92(2): 556-62, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19235214

RESUMEN

Particle-induced osteolysis is a major cause of aseptic loosening after total joint replacement. The purpose of the current study was to evaluate the DNA damage repair capacity of macrophages in patients with aseptic hip loosening by determination of ERCC1. Moreover, we wanted to elucidate if the potency of the DNA-repair mechanisms correlates with the survival of joint implants. For this purpose we compared the immunohistochemical ERCC1 expression in capsules and interface membranes of patients with loosening of a hip replacement in the first 10 years after implantation with those in patients with late loosening. In analogy with ERCC1 studies on cancer in humans we calculated the semi-quantitative H-score by multiplying the staining intensity with the proportion score of positive stained macrophages. The level of ERCC1 reaction in the specimens taken from patients with early aseptic loosening (mean H-score 0.57) was clearly lower in comparison with those from patients undergoing exchange hip arthroplasty later than 10 years after surgery (mean H-score 2.24). We determined an H-score for ERCC1 expression of 1 as a cutoff point giving a sensitivity and specificity of 100% for identification of early aseptic loosening after less than 10 years. In summary, lower levels of ERCC1 were found in patients with early aseptic loosening compared to patients with aseptic loosening later than 10 years.


Asunto(s)
Proteínas de Unión al ADN/biosíntesis , Endonucleasas/biosíntesis , Prótesis de Cadera , Falla de Prótesis , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera , Autopsia , Recuento de Células , Colorantes , Daño del ADN , Proteínas de Unión al ADN/genética , Endonucleasas/genética , Femenino , Articulación de la Cadera/citología , Articulación de la Cadera/patología , Humanos , Inmunohistoquímica , Cápsula Articular/citología , Cápsula Articular/patología , Macrófagos/fisiología , Masculino , Persona de Mediana Edad , Curva ROC , Análisis de Supervivencia , Fijación del Tejido
3.
Int J Biol Sci ; 5(2): 182-91, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19214244

RESUMEN

Particle-induced osteolysis is a major cause of aseptic loosening after total joint replacement. While the osteolytic cascade initiated by cytokine release from macrophages has been studied extensively, the involvement of T-lymphocytes in this context is controversial and has been addressed by only a few authors. In a former study we detected that the quantity of T-lymphocytes may be influenced by apoptosis in patients with aseptic loosening. In this study we intended to find out more details about the apoptosis-induced shifting of the T-cell number. We focused our interest on the CD4(+) and CD8(+) T-cells and their relative ratio. Caspase-3 cleaved was evaluated immunohistochemically to detect apoptotic T-cells in capsules and interface membranes from patients with aseptic hip implant loosening and a varying degree of caspase-3 cleaved expression in CD4(+) and CD8(+) T-lymphocytes was detected. Moreover, a relationship between the intensity of the apoptotic reactions and the radiological extent of osteolysis was observed. The number of CD4(+) cells was decreased in the presence of strong apoptotic reactions, respectively extensive osteolysis, while CD8(+) cells were affected to a much lower degree. Thus, the CD4(+)/CD8(+) ratio changed from 1.0 in cases with only small areas of periprosthetic osteolysis and minimally intense apoptosis to 0.33 in cases with large areas of osteolysis. This may suggest a causal relationship between the apoptosis-induced shift in the CD4(+)/CD8(+) ratio and the osteolysis respectively aseptic loosening. It is possible that these findings may lead to a new understanding of particle-induced osteolysis.


Asunto(s)
Apoptosis , Artroplastia de Reemplazo de Cadera/efectos adversos , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Prótesis de Cadera/efectos adversos , Anciano , Anciano de 80 o más Años , Caspasa 3/metabolismo , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Osteólisis/etiología
4.
Apoptosis ; 14(2): 173-81, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19130234

RESUMEN

Particle-induced osteolysis is a major cause of aseptic loosening after total joint replacement. Earlier studies demonstrated apoptotic macrophages, giant cells, fibroblasts and T-lymphocytes in capsules and interface membranes of patients with aseptic hip implant loosening. The aim of the current study was to determine in a murine calvarial model of wear particle-induced osteolysis whether inhibition of apoptosis using the pan-caspase inhibitor BOC-D-FMK reduces aseptic loosening. Healthy 12-week-old male C57BL/6J mice were treated with UHMWPE particles and received a daily peritoneal injection of BOK-D-FMK, respectively only buffer at a dose of 3 mg/kg of body weight for 12 days until sacrifice. Bone resorption was measured by histomorphometry, micro CT (computed tomography) and TRAP-5b serum analysis. Apoptosis was measured using caspase-3 cleaved staining. The results demonstrated that UHMWPE particles induced stronger apoptotic reactions in macrophages and osteoblasts and increased bone resorption in non-specifically treated mice, whereas peritoneal application of BOC-D-FMK significantly counteracted these adverse particle-related effects. We think that in particle-induced osteolysis apoptosis is pathologically increased, and that failure to reduce the quantity of apoptotic bodies leads to an up-regulation of proinflammatory cytokines, which may be responsible for the induction of osteolysis. We showed for the first time in vivo that a reduction in apoptosis leads to a significant reduction in particle-induced osteolysis. Clinically, the apoptotic cascade could become an interesting novel therapeutic target to modulate particle-induced osteolysis.


Asunto(s)
Compuestos de Bencilo/farmacología , Inhibidores de Caspasas , Hidrocarburos Fluorados/farmacología , Osteólisis/enzimología , Osteólisis/prevención & control , Fosfatasa Ácida/sangre , Animales , Caspasa 3/metabolismo , Inmunohistoquímica , Isoenzimas/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Tamaño de los Órganos , Osteoclastos/efectos de los fármacos , Osteoclastos/patología , Osteólisis/sangre , Osteólisis/inducido químicamente , Polietilenos , Implantación de Prótesis , Cráneo/diagnóstico por imagen , Cráneo/efectos de los fármacos , Cráneo/enzimología , Cráneo/patología , Fosfatasa Ácida Tartratorresistente , Microtomografía por Rayos X
5.
J Biomed Mater Res A ; 89(3): 707-16, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18449944

RESUMEN

Particle-induced osteolysis is the most frequent cause of aseptic loosening after total joint replacement. We performed a study to illuminate the effect of ceramic particles with different diameters and concentrations on the mRNA expression of certain key regulators in particle-induced aseptic osteolysis (RANK, RANKL, OPG, and TNF-alpha) in THP-1 macrophage-like cells. Titanium particles were used as a positive control. RNA was analyzed by quantitative RTPCR. Our results demonstrate that alumina ceramic particles, regardless of particle size, caused only slight upregulations of RANK, TNF-alpha, and OPG mRNA, whose levels were significantly lower in comparison with those of titanium particles (p < 0.05). The continuous increasing tendency to time and particle-dependent mRNA expression of all the parameters stimulated by titanium particles was not found after stimulation with ceramic materials. Even after the concentration of ceramic particles was increased, only a mild upregulation of mRNA expression was found. Furthermore, we observed that the bioinert properties of ceramic particles did not change much in diameters ranging from 0.5 to 1.5 microm. At most of the measuring time points, there was no significant difference between the reactions of the large and small particles in this range. Our results support the theory about the relative bioinert properties of alumina ceramic particles.


Asunto(s)
Óxido de Aluminio/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Monocitos/metabolismo , Osteoprotegerina/genética , Receptor Activador del Factor Nuclear kappa-B/genética , Titanio/farmacología , Factor de Necrosis Tumoral alfa/genética , Línea Celular , Humanos , Monocitos/efectos de los fármacos , Osteoprotegerina/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptor Activador del Factor Nuclear kappa-B/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
6.
Eur Spine J ; 17(10): 1362-72, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18704516

RESUMEN

A considerable number of patients complain about pain after lumbar surgery. The spinal dura mater has been debated as a possible source of this pain. However, there is no information if laminectomy influences the nociceptive sensory innervation of the dura. Therefore, we quantitatively evaluated the density of SP- and CGRP-immunopositive nerve fibers in the dura mater lumbalis in an animal model of laminectomy. Twelve adult Lewis rats underwent laminectomy, in six of them the exposed dura was covered by an autologous fat graft. Further six animals without surgical treatment served as controls. Six weeks after surgery, the animals were perfused and the lumbar dura was processed immunohistochemically for the detection of CGRP- and SP-containing nerve fibers. In controls, the peptidergic nerve fibers were found predominantly in the ventral but rarely in the dorsal dura mater lumbalis. After laminectomy, the density of SP- and CGRP-immunopositive neurons significantly increased in ventral as well as in dorsal parts of the dura. Axonal spines could be observed in some cases at the site of laminectomy. The application of autologous fat grafts failed to inhibit the significant increase in the density of peptidergic afferents. Thus, we have provided the first evidence that laminectomies induce an increase in the density of putative nociceptive SP- and CGRP-immunopositive neurons in the lumbar dura mater ascribable to an axonal sprouting of fine nerve fibers. This effect was not prevented by using autologous fat grafts. It is conceivable that the neuronal outgrowth of nociceptive afferents is a cause of low back pain observed after lumbar surgery.


Asunto(s)
Tejido Adiposo/trasplante , Duramadre/citología , Laminectomía/efectos adversos , Nociceptores/citología , Complicaciones Posoperatorias , Animales , Péptido Relacionado con Gen de Calcitonina/metabolismo , Duramadre/metabolismo , Duramadre/cirugía , Inmunohistoquímica , Dolor de la Región Lumbar/etiología , Región Lumbosacra , Masculino , Fibras Nerviosas/metabolismo , Nociceptores/metabolismo , Ratas , Ratas Endogámicas Lew , Médula Espinal/metabolismo , Médula Espinal/cirugía , Sustancia P/metabolismo
7.
Biomaterials ; 29(24-25): 3444-50, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18490052

RESUMEN

Particle-induced osteolysis is a major cause of aseptic loosening after total joint replacement. The purpose of the current study was to identify various apoptosis-related pathways in the cellular response to wear debris. Fas receptor, BAK and caspase-3 cleaved were evaluated immunohistochemically in capsules and interface membranes from patients with aseptic hip implant loosening. Moreover, we investigated local cellular proliferation, documented by the presence of Ki-67, to evaluate the proportion of apoptosis in relation to the proliferation in the different cells. We detected a strong expression of caspase-3 cleaved, Fas and BAK in macrophages, giant cells and T-lymphocytes. The fibroblasts showed caspase-3 cleaved and BAK, but no Fas staining. Demonstrated by Ki-67 staining, we found increased proliferation of macrophages and fibroblasts. Statistical analysis showed a significant positive correlation (p<0.001) between the above mentioned results and the presence of wear debris. The intensity of apoptosis and proliferation differed, depending on the extent of osteolysis. Overall, four different patterns of immunoreactivity were identified. We think, however, that in particle-induced osteolysis apoptosis is pathologically increased - a phenomenon also seen in other diseases. In these instances, the number and degree of apoptotic reactions are so great that the resulting cell remains cannot be completely removed. This leads to an increased excretion of fibrogenic mediators that could be responsible for increased proliferation of fibroblasts in spite of the increased apoptosis. Moreover, it leads to an increased excretion of cytokines which could be responsible for the activation of osteoclasts.


Asunto(s)
Apoptosis/fisiología , Artroplastia de Reemplazo de Cadera/efectos adversos , Prótesis de Cadera/efectos adversos , Osteólisis/etiología , Adulto , Anciano , Anciano de 80 o más Años , Caspasa 3/análisis , Proliferación Celular , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Macrófagos/citología , Macrófagos/metabolismo , Masculino , Persona de Mediana Edad , Proteína Destructora del Antagonista Homólogo bcl-2/análisis , Receptor fas/análisis
8.
J Mater Sci Mater Med ; 19(1): 417-24, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17607522

RESUMEN

In revision hip replacement surgery cortical strut grafts made of allograft bone are used to augment femoral bone stock and to fix periprosthetic femoral fractures. These struts are made from femoral bone as hemi-cylinders and are fixed to host bone with cerclage wires. We developed an artificial bone substitute for such strut grafts in order to overcome availability restrictions and potential infectious hazards with allograft bone. The partially biodegradable implant consists of a functionally-graded combination of titanium, polylactide, hydroxyapatite, and calcium carbonate. It is made by manual dip-coating of the metal (after chemical surface treatment) into solutions of polylactide with suspended calcium salts. In this way the titanium core is surrounded by an inner layer of slowly biodegradable poly(L-lactide) with calcium carbonate. The part of the implant that is in contact with the bone consists of rapidly biodegradable poly(D,L-lactide), hydroxyapatite and calcium carbonate. This method leads to an implant which is easily adaptable before the implantation to the geometry of the patient's bone when moderately heated (70 degrees C), but has a sufficient mechanical strength to serve as support under physiologic temperatures. The implant is mechanically stable, biocompatible, partially biodegradable, and provides a scaffold for growing bone.


Asunto(s)
Materiales Biocompatibles/química , Sustitutos de Huesos/química , Trasplante Óseo/métodos , Metales/química , Polímeros/química , Titanio/química , Durapatita/química , Diseño de Equipo , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Poliésteres/química , Temperatura , Tomografía Computarizada por Rayos X/métodos , Trasplante Homólogo
9.
Arch Orthop Trauma Surg ; 128(6): 545-50, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18000673

RESUMEN

The treatment of acetabular bone defects presents a great challenge in revision total hip arthroplasty (THA). The purpose of this study was to evaluate the clinical and radiological outcome of revision THA using jumbo cups for acetabular reconstruction after applying the bone-grafting technique. We studied 17 patients with acetabular defects ranging from Type 2A to Type 3A according to Paprosky's classification. According to the AAOS-score twelve patients were classified as Type II and five patients as Type III. Uncemented press-fit cups with an outer diameter larger than 64 mm were used in all cases. Fifteen patients received morselized bone allografts. In eight patients an additional screw fixation was necessary. The mean follow-up period was 82 months (range 33-149). The mean Harris Hip Score was preoperatively 62 and at the time of the last follow-up examination 83 points (p = 0.007). Two acetabular components failed, one due to aseptic loosening and another one due to septic loosening. There was a trend of displacement of the femoral head centre towards the infero-lateral position after using jumbo cups that approached statistical significance (p = 0.065). Closure of acetabular defects of Types 2A to 3A according to Paprosky's classification and type II to III according to the AAOS-score respectively can be satisfactorily accomplished using jumbo cups after applying the bone-grafting technique.


Asunto(s)
Acetábulo , Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Adulto , Anciano , Femenino , Cabeza Femoral , Humanos , Inestabilidad de la Articulación , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Rango del Movimiento Articular , Proyectos de Investigación , Estudios Retrospectivos
10.
Calcif Tissue Int ; 81(5): 394-402, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17952672

RESUMEN

Small-animal models are useful for the in vivo study of particle-induced osteolysis, the most frequent cause of aseptic loosening after total joint replacement. Microstructural changes associated with particle-induced osteolysis have been extensively explored using two-dimensional (2D) techniques. However, relatively little is known regarding the 3D dynamic microstructure of particle-induced osteolysis. Therefore, we tested micro-computed tomography (micro-CT) as a novel tool for 3D analysis of wear debris-mediated osteolysis in a small-animal model of particle-induced osteolysis. The murine calvarial model based on polyethylene particles was utilized in 14 C57BL/J6 mice randomly divided into two groups. Group 1 received sham surgery, and group 2 was treated with polyethylene particles. We performed 3D micro-CT analysis and histological assessment. Various bone morphometric parameters were assessed. Regression was used to examine the relation between the results achieved by the two methods. Micro-CT analysis provides a fully automated means to quantify bone destruction in a mouse model of particle-induced osteolysis. This method revealed that the osteolytic lesions in calvaria in the experimental group were affected irregularly compared to the rather even distribution of osteolysis in the control group. This is an observation which would have been missed if histomorphometric analysis only had been performed, leading to false assessment of the actual situation. These irregularities seen by micro-CT analysis provide new insight into individual bone changes which might otherwise be overlooked by histological analysis and can be used as baseline information on which future studies can be designed.


Asunto(s)
Prótesis Articulares/efectos adversos , Osteólisis/diagnóstico por imagen , Osteólisis/fisiopatología , Falla de Prótesis , Tomografía Computarizada por Rayos X/métodos , Animales , Materiales Biocompatibles/efectos adversos , Resorción Ósea/diagnóstico por imagen , Resorción Ósea/etiología , Resorción Ósea/fisiopatología , Sustitutos de Huesos/efectos adversos , Modelos Animales de Enfermedad , Reacción a Cuerpo Extraño/diagnóstico por imagen , Reacción a Cuerpo Extraño/patología , Reacción a Cuerpo Extraño/fisiopatología , Masculino , Ensayo de Materiales/métodos , Ratones , Osteólisis/etiología , Osteonecrosis/diagnóstico por imagen , Osteonecrosis/patología , Osteonecrosis/fisiopatología , Polietileno/efectos adversos , Valor Predictivo de las Pruebas , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Sensibilidad y Especificidad , Cráneo/diagnóstico por imagen , Cráneo/patología , Cráneo/fisiopatología
11.
J Bone Miner Res ; 22(7): 1011-9, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17419680

RESUMEN

UNLABELLED: This study investigates the impact of alpha-CGRP on bone metabolism after implantation of polyethylene particles. alpha-CGRP knockout mice showed less osteolysis compared with wildtype mice. The local neurogenic microenvironment might be a crucial factor in particle-induced osteolysis. INTRODUCTION: Periprosthetic osteolysis is the major reason for aseptic loosening in joint arthroplasty. This study aimed to investigate the potential impact of alpha-calcitonin gene-related peptide (alpha-CGRP) deficiency on bone metabolism under conditions of polyethylene particle-induced osteolysis. MATERIALS AND METHODS: We used the murine calvarial osteolysis model based on polyethylene particles in 14 C57BL 6 mice and 14 alpha-CGRP-deficient mice divided into four groups of 7 mice each. Groups 1 (C57BL/J 6) and 3 (alpha-CGRP knockout) received sham surgery, and groups 2 (C57BL/J 6) and 4 (alpha-CGRP knockout) were treated with polyethylene particles. Qualitative and quantitative 3D analyses were performed using microCT. In addition, bone resorption was measured within the midline suture by histological examination. The number of osteoclasts was determined by counting the TRACP(+) cells. Calvarial bone was tested for RANKL expression by RT-PCR and immunocytochemistry. RESULTS: Bone resorption was significantly reduced in alpha-CGRP-deficient mice compared with their corresponding wildtype C57BL 6 mice as confirmed by histomorphometric data (p < 0.001) and microCT (p < 0.01). Osteoclast numbers were significantly reduced in group 3 and the particle subgroup compared with group 1 (p < 0.001). We observed a >3-fold increase of basal RANKL mRNA levels within group 1 compared with group 3. Additional low RANKL immunochemistry staining was noted in groups 3 and 4. CONCLUSIONS: In conclusion, alpha-CGRP knockout mice did not show the expected extended osteolysis compared with wildtype mice expressing alpha-CGRP. One of the most reasonable explanations for the observed decrease in osteolysis could be linked to the osteoprotegerin (OPG)/RANK/RANKL system in alpha-CGRP-deficient animals. As a consequence, the fine tuning of osteoclasts mediating resorption in alpha-CGRP-null mice may be deregulated.


Asunto(s)
Resorción Ósea/patología , Péptido Relacionado con Gen de Calcitonina/deficiencia , Polietileno/farmacología , Fosfatasa Ácida/metabolismo , Animales , Resorción Ósea/inducido químicamente , Recuento de Células , Inmunohistoquímica , Implantes Experimentales , Isoenzimas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Ligando RANK/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Cráneo/efectos de los fármacos , Cráneo/patología , Fosfatasa Ácida Tartratorresistente , Tomografía Computarizada por Rayos X
12.
Eur J Pain ; 11(1): 67-74, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16460974

RESUMEN

Using immunohistochemical methods we determined the presence of SP- and CGRP-immunopositive nerve fibers in the hip joint of patients with femoral neck fracture (controls, group 1), painful osteoarthritis (group 2), and painless failed total hip arthroplasties (group 3). Immunoreactive nerve fibers were found in the soft tissue of the fossa acetabuli as well as in the subintimal part of the synovial layer in the hip joint capsule of groups 1 and 2. In the capsule of controls the innervation density had a median of 5.7fibers/cm(2) for CGRP-ir and 3.2fibers/cm(2) for SP-ir afferents. In the osteoarthritic group, the density significantly increased to a median of 15.6fibers/cm(2) for CGRP-ir and 8.2fibers/cm(2) for SP-ir neurons (p=0.05). Patients with failed hip arthroplasties completely lacked these neuropeptide containing afferents. Innervation density in the fossa acetabuli of osteoarthritc patients showed a median of 14.1fibers/cm(2) for CGRP-ir and 5.9fibers/cm(2) for SP-ir afferents. From these data we assume that the hip joint capsule and the soft tissue of the fossa acetabuli are important triggers of nociception. This is supported by the fact, that patients with loosened total hip arthroplasties, where we failed to detect SP- and CGRP-immunoreactive fibers, did not feel pain. The upregulation of SP- and CGRP-positive neurons in response to arthritic stages suggests a mechanism involving neuropeptides in the maintenance of a painful degenerative joint disease and in mediating noxious stimuli from the periphery. Furthermore, these findings help to explain clinical observations, such as effectiveness of local therapy to control hip pain with intraarticular injection, synovectomy and denervation procedures.


Asunto(s)
Articulación de la Cadera/inervación , Articulación de la Cadera/fisiopatología , Neuropéptidos/metabolismo , Nociceptores/metabolismo , Osteoartritis de la Cadera/fisiopatología , Células Receptoras Sensoriales/metabolismo , Anciano , Artroplastia de Reemplazo de Cadera/efectos adversos , Péptido Relacionado con Gen de Calcitonina/metabolismo , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Nociceptores/citología , Osteoartritis de la Cadera/metabolismo , Dolor/etiología , Dolor/fisiopatología , Dolor Intratable/etiología , Dolor Intratable/metabolismo , Dolor Intratable/fisiopatología , Complicaciones Posoperatorias/fisiopatología , Células Receptoras Sensoriales/citología , Sustancia P/metabolismo , Membrana Sinovial/inervación , Membrana Sinovial/fisiopatología , Regulación hacia Arriba/fisiología
13.
Biomed Tech (Berl) ; 51(1): 21-6, 2006 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-16771126

RESUMEN

AIM: Does the pressfit anchorage of cementless acetabular cups depend on the roughness of the pole? To answer this question the primary pressfit of two cementless acetabular cups which differ only with regard to the roughness of their poles were compared by means of finite elements analysis. MATERIALS AND METHODS: It was assumed that the material properties of bone are homogeneous, isotropic and linearly elastic. Material-specific values of cancellous bone with three different bone densities were used. Assumption of isotropy represents an approximation. RESULTS: Comparison of the two prosthesis designs revealed that both designs/shapes cause similar patterns of bone deformation and tension. CONCLUSIONS: It can therefore be concluded that with regard to pressfit anchorage the prosthesis with milled polar surface is according to FEA mechanically equivalent to the prosthesis with non-milled polar surface.


Asunto(s)
Acetábulo/fisiología , Artroplastia de Reemplazo de Cadera/instrumentación , Artroplastia de Reemplazo de Cadera/métodos , Diseño Asistido por Computadora , Análisis de Falla de Equipo/métodos , Acetábulo/cirugía , Cementación , Análisis de Elementos Finitos , Fricción , Dureza , Humanos , Presión , Diseño de Prótesis , Estrés Mecánico , Propiedades de Superficie
14.
Biomaterials ; 27(15): 3010-20, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16445975

RESUMEN

Particle-induced osteolysis is a major cause of aseptic loosening after total joint replacement. The possible induction of apoptosis has not been addressed in great detail. Thus far, it has been shown that ceramic and polyethylene particles can induce apoptosis of macrophages in vitro. The purpose of this study was to test the hypothesis that wears debris generated from total hip arthroplasty could induce cellular damage and apoptosis in vivo. We therefore determined by immunohistochemical methods if increased expression of p53, an important transcription factor, and BAK and Bcl-2, two important regulators of apoptosis, can be found in interface membranes and capsules of hips with aseptically loose implants. Strongly positive immunohistochemical staining for p53 and BAK was found in peri-implant tissues from patients with aseptic hip implant loosening. Differentiation of various cell types showed that macrophages stained positive for p53 in all capsule and interface specimens. p53 was frequently detected in giant cells. Positive staining of BAK in macrophages and giant cells was seen in all specimens. Some positive reactions were observed in fibroblasts, only two of 19 cases stained for p53 and three cases for BAK within synovial cells. Positive macrophages and giant cells were localized around polyethylene particles. While T-lymphocytes showed a regular BAK-staining, the other leukocytes were negative. Statistical analyses showed significant positive correlations (p < 0.001) between the presence of polyethylene and metal debris and the expression of BAK and p53. Polyethylene particles were surrounded by more positive macrophages and giant cells than were metal particles, indicating that polyethylene debris may be a stronger inductor of cell cycle arrest and apoptosis than metal debris. In this study apoptosis of macrophages, giant cells and T-lymphocytes in capsules and interface membranes of patients with aseptic hip implant loosening has been demonstrated in vivo. It is possible that the apoptotic cascade could evolve as a novel therapeutic target to prevent particle-induced osteolysis.


Asunto(s)
Reacción a Cuerpo Extraño/metabolismo , Articulación de la Cadera/metabolismo , Inestabilidad de la Articulación/metabolismo , Macrófagos/metabolismo , Infecciones Relacionadas con Prótesis/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteína Destructora del Antagonista Homólogo bcl-2/metabolismo , Adulto , Anciano , Artroplastia de Reemplazo de Cadera/efectos adversos , Células Cultivadas , Femenino , Reacción a Cuerpo Extraño/etiología , Articulación de la Cadera/cirugía , Humanos , Inestabilidad de la Articulación/etiología , Masculino , Persona de Mediana Edad , Infecciones Relacionadas con Prótesis/etiología
15.
J Biomed Mater Res A ; 75(2): 288-94, 2005 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-16088891

RESUMEN

Alterations of the key regulators of osteoclastogenesis, receptor activator of NF-kappaB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) have been implicated in wear particle-induced osteolysis, the most common cause for implant failure in total joint replacements. This study investigated the effect of exogenous OPG on ultra-high-molecular-weight polyethylene (UHMWPE) particle-induced osteolysis. The murine calvarial osteolysis model was utilized in 28 C57BL/6J mice randomized to four groups. Group I underwent sham surgery only, group II received UHMWPE particles, and group III and IV particles and subcutaneous OPG starting from day 0 (group III) or day 5 (group IV) until sacrifice. After 2 weeks, calvaria were prepared for histology and histomorphometry. Bone resorption was measured within the midline suture using Giemsa staining and osteoclast numbers were determined using TRAP staining. UHMWPE particle implantation resulted in grossly pronounced osteoclastogenesis and bone resorption. Both immediate and delayed treatment with OPG counteracted these particle-induced effects significantly, suppressing osteoclast formation and bone resorption (p < 0.001 and p < 0.001, respectively). In conclusion, exogenous OPG markedly suppressed UHMWPE particle-induced osteolysis in a murine calvarial model. This important finding underscores the crucial significance of the OPG-RANKL-RANK signaling in wear particle-induced osteolysis. Exogenous OPG may prove an effective treatment modality for wear debris-mediated periprosthetic osteolysis after total joint arthroplasty.


Asunto(s)
Glicoproteínas/metabolismo , Osteólisis , Polietilenos/metabolismo , Falla de Prótesis , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores del Factor de Necrosis Tumoral/metabolismo , Animales , Materiales Biocompatibles/metabolismo , Femenino , Glicoproteínas/administración & dosificación , Masculino , Ensayo de Materiales , Ratones , Ratones Endogámicos C57BL , Modelos Biológicos , Osteoclastos/citología , Osteoclastos/metabolismo , Osteoprotegerina , Tamaño de la Partícula , Distribución Aleatoria , Receptores Citoplasmáticos y Nucleares/administración & dosificación , Receptores del Factor de Necrosis Tumoral/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/metabolismo , Cráneo/citología
16.
Biomed Tech (Berl) ; 50(5): 143-7, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15966619

RESUMEN

The value of plain radiographs, digital subtraction arthrography and radionuclide arthrography was analysed in 23 cases of failed total knee arthroplasty. The preoperative diagnosis was compared with the intraoperative assessment. Sensitivity, specificity and the positive and negative predictive value for assessing a loose component were determined separately for the femoral and tibial components. At revision we found 13 loose femoral and 12 loose tibial implants. In eight cases both components were unstable. Plain radiography had a sensitivity of 77% for loosening of the femoral and 83% for the tibial component; digital subtraction arthrography 77% for the femoral and 8% for the tibial component and radionuclide arthrography 31% and 8%. The specificity for plain radiography was 90% for the femoral and 72% for the tibial implant. For subtraction arthrography it was 50% and 82% and for subtraction arthrography 70% and 82%. Radiography had the highest positive and negative predictive values for both components compared with the other two techniques. As a diagnostic tool to detect implant loosening, plain radiography is the most effective in this study. Subtraction arthrography and radionuclide arthrography are not suitable for use as routine methods for detection of total knee arthroplasty loosening.


Asunto(s)
Artrografía/métodos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Análisis de Falla de Equipo/métodos , Inestabilidad de la Articulación/diagnóstico por imagen , Medición de Riesgo/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inestabilidad de la Articulación/etiología , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Falla de Prótesis , Cintigrafía , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y Especificidad , Técnica de Sustracción , Resultado del Tratamiento
17.
Biomaterials ; 26(29): 5783-9, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15869791

RESUMEN

The effects of statins on bone formation in periprosthetic osteolysis have not been determined to date. We investigated the effect of the HMG-CoA reductase inhibitor simvastatin on osteoblastic bone formation under conditions of ultra-high molecular weight polyethylene (UHMWPE) particle-induced osteolysis. The murine calvarial osteolysis model was utilized in 21 C57BL/J6 mice randomized to three groups. Group I underwent sham surgery only, group II received UHMWPE particles, and group III, particles and simvastatin treatment. After 2 weeks, calvaria were processed for histomorphometry and stained with Giemsa dye. New bone formation was measured as osteoid tissue area within the midline suture. Bone thickness was quantified as indicator of net bone growth. Statistical analysis was performed using one-way ANOVA and a Student's t-test. New bone formation and bone thickness were significantly enhanced following simvastatin treatment. New bone formation was 0.008+/-0.008 mm2 in sham controls (group I), 0.015+/-0.012 mm2 after particle implantation without further intervention (group II), compared to 0.083+/-0.021 mm2 with particle implantation and simvastatin treatment (group III) (p=0.003). The bone thickness was 0.213+/-0.007 mm in group I, 0.183+/-0.005 mm in group II, and 0.238+/-0.009 mm in group III (p=0.00008). In conclusion, simvastatin treatment markedly promoted bone formation and net bone growth in UHMWPE particle-induced osteolysis in a murine calvarial model. These new findings indicate that simvastatin may have favorable osteoanabolic effects on wear debris-mediated osteolysis after total joint arthroplasty, involving local stimulation of osteoblastic bone formation.


Asunto(s)
Sustitutos de Huesos/química , Osteogénesis , Polietileno/química , Simvastatina/química , Animales , Colorantes Azulados/farmacología , Huesos/efectos de los fármacos , Femenino , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Masculino , Ensayo de Materiales , Ratones , Ratones Endogámicos C57BL , Microscopía Electrónica de Rastreo , Osteólisis , Polietilenos , Falla de Prótesis , Simvastatina/farmacología , Estrés Mecánico
18.
Biomaterials ; 26(17): 3549-55, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15621245

RESUMEN

This study aimed to investigate the effects of the HMG-CoA reductase inhibitor simvastatin on ultra-high molecular weight polyethylene (UHMWPE) particle-induced osteolysis. The murine calvarial osteolysis model was used in 21 C57BL/J6 mice randomized to three groups. Group I underwent sham surgery only, group II received UHMWPE particles, and group III, particles and simvastatin treatment. After two weeks, calvaria were processed for histomorphometry. Bone resorption was measured as resorption within the midline suture using Giemsa staining. Osteoclast numbers were determined per high-power field using TRAP-staining. Statistical analysis was performed using one-way ANOVA and Student's t-test. Bone resorption in midline suture was 0.094+/-0.007 mm(2) in sham controls (group I), 0.25+/-0.025 mm(2) after particle implantation without further intervention (group II), and 0.131+/-0.02 mm(2) with particle implantation and additional simvastatin treatment (group III) (p=0.00003). Osteoclast numbers were 15.3+/-3.6 in group I, 48.7+/-7.1 in group II and 6.2+/-3.1 in group III (p=0.00002). In conclusion, simvastatin treatment markedly decreased UHMWPE particle-induced osteolysis in a murine calvarial model. This finding suggests that simvastatin may have a role for noninvasive prevention and treatment of wear debris-mediated periprosthetic osteolysis after total joint arthroplasty.


Asunto(s)
Osteólisis/inducido químicamente , Osteólisis/prevención & control , Polietilenos/efectos adversos , Infecciones Relacionadas con Prótesis/inducido químicamente , Infecciones Relacionadas con Prótesis/prevención & control , Simvastatina/administración & dosificación , Cráneo/efectos de los fármacos , Animales , Materiales Biocompatibles/efectos adversos , Femenino , Ensayo de Materiales , Ratones , Ratones Endogámicos C57BL , Osteólisis/patología , Tamaño de la Partícula , Falla de Prótesis , Cráneo/patología , Cráneo/cirugía , Resultado del Tratamiento
19.
Biomaterials ; 26(17): 3719-25, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15621262

RESUMEN

We investigated the effect of a single subcutaneous dose of zoledronic acid on particle-induced osteolysis and observed excessive regional new bone formation. We utilized the murine calvarial osteolysis model and polyethylene particles in C57BL/J6 mice. Twenty-eight mice were used, seven per group. Specimens were stained with Giemsa dye. The osteoid tissue area was determined. Bone thickness was measured as an indicator of bone growth. Net bone growth was significantly increased in animals with zoledronic acid treatment: 0.02 mm(2)+/-0.03 mm(2) in animals with particle implantation only (group 2), 0.25 mm(2)+/-0.08 mm(2) with particle implantation and zoledronic acid treatment directly after surgery (group 3; p=0.0018), and 0.21 mm(2)+/-0.11 mm(2) with particle implantation and zoledronic acid treatment on the fourth postoperative day (group 4; p=0.0042). The mean bone thickness was 0.2 mm+/-0.04 mm (range 0.17 mm-0.31 mm) in group 1 (sham controls) and 0.16 mm+/-0.02 mm (range 0.14 mm-0.19 mm) in group 2, 0.31 mm+/-0.04 mm (range 0.28 mm-0.39 mm) in group 3, and 0.29 mm+/-0.02 mm (range 0.28 mm-0.34 mm) in group 4. Student's t-test revealed a statistically significant difference between groups 2 and 3 (p=0.00042), and groups 2 and 4 (p=0.0019). In conclusion, our observational study suggests that zoledronic acid may stimulate bone apposition locally in the process of particle-induced osteolysis.


Asunto(s)
Difosfonatos/administración & dosificación , Imidazoles/administración & dosificación , Osteogénesis/efectos de los fármacos , Osteólisis/patología , Osteólisis/prevención & control , Polietilenos/efectos adversos , Cráneo/efectos de los fármacos , Cráneo/patología , Animales , Reacción a Cuerpo Extraño/inducido químicamente , Reacción a Cuerpo Extraño/patología , Reacción a Cuerpo Extraño/prevención & control , Ratones , Ratones Endogámicos C57BL , Osteólisis/inducido químicamente , Tamaño de la Partícula , Falla de Prótesis , Infecciones Relacionadas con Prótesis/inducido químicamente , Infecciones Relacionadas con Prótesis/prevención & control , Resultado del Tratamiento , Ácido Zoledrónico
20.
Biomaterials ; 26(14): 1803-8, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15576154

RESUMEN

The most common cause of implant failure in joint replacement is aseptic loosening due to particle-induced osteolysis. Bisphosphonates have been shown to be effective against particle-induced osteolysis when administered daily. We investigated the effect of a single subcutaneous dose of a more potent third generation bisphosphonate on particle-induced osteolysis. We utilized the murine calvaria osteolysis model in C57BL/J6 mice. Bone resorption was measured as resorption within the midline suture using Giemsa staining. Twenty-eight mice were used, seven per group. Seven animals were treated with a single dose of zoledronic acid (ZA) directly after surgery and seven animals were treated four days postoperatively. For statistical analysis one-way ANOVA and a Student's t-test were used. Bone resorption was 0.26+/-0.09 mm(2) in animals with particle implantation, 0.14+/-0.05 mm(2) in animals with particle implantation and ZA treatment directly after surgery (p = 0.0047), and 0.15+/-0.05 mm(2) in animals with particle implantation and ZA treatment on the fourth postoperative day (p = 0.006). In conclusion, particle-induced bone resorption was markedly decreased by a single s.c. dose of a third generation bisphosphonate. This important new finding holds great promise, because single dose treatment of particle-induced osteolysis may reduce side effects compared to repeated application of bisphosphonates.


Asunto(s)
Materiales Biocompatibles/efectos adversos , Difosfonatos/administración & dosificación , Reacción a Cuerpo Extraño/tratamiento farmacológico , Reacción a Cuerpo Extraño/patología , Imidazoles/administración & dosificación , Osteólisis/tratamiento farmacológico , Osteólisis/patología , Polietileno/efectos adversos , Animales , Femenino , Reacción a Cuerpo Extraño/etiología , Inyecciones Subcutáneas , Masculino , Ensayo de Materiales , Ratones , Ratones Endogámicos C57BL , Osteólisis/etiología , Osteólisis/prevención & control , Tamaño de la Partícula , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Ácido Zoledrónico
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