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No description available.

Periacetabular osteolysis is a significant complication following total hip replacement surgery. It is believed to be caused by wear debris and high fluid pressures within the joint capsule. To investigate the mechanisms by which high fluid pressures are generated in total hip replacement, a physical model of the hip joint was constructed, the Acetabular Pressure Transmission Rig (APTR). An aluminium chamber held the bone analogue, a polyurethane hemisphere with a 52mm acetabular cavity, and the prosthetic components, a 28mm femoral head and various uncemented cups, were inserted without press-fit to simulate cup loosening. A synovial fluid analogue was introduced into the chamber through an elevated reservoir. Rigid transmission tubes conducted fluid pressures from the cup-cavity interface to external transducers. The APTR was loaded under various conditions and the pressures produced by the loading regimes were analysed. Pressures over 35kPa, previously shown by other groups to cause osteolysis, were measured within the APTR, reaching a maximum of 131.3kPa measured at the pole of the cup. Changes in load application led to pressure changes within the APTR, with higher loading frequency and magnitude leading to higher median pressure amplitudes. The presence of different component features, such as screw holes in the metal shell, was also shown to affect periacetabular pressures. Tests with a fibrous rim interposed between the prosthetic cup and the test cavity showed an 88% reduction in periacetabular pressures, as the increased rim interference between cup and cavity prevented fluid ingress behind the cup. A larger initial separation between the loading head and the acetabular cup caused a significant increase in measured pressures, with a 0.15mm increase in head-cup separation producing a 53% increase in pressures measured at the pole of the cup. Pressure differentials between different transducer sites indicated the ability for fluid flow behind the cup, which can be related in vivo to the movement of particulate debris to periacetabular bone. The APTR was able to measure clinically significant pressures and to analyse the effects of modifying component and loading characteristics with currently available prosthetic components. This makes the rig useful in a clinical context, as it has been shown to be capable of testing a broad range of component types under a wide range of conditions. Its use will ensure new prostheses and fixation modes can be designed in such a way as to eliminate the damaging fluid pressures currently observed in artificial hip joint replacements.

Breast cancer most commonly metastasizes to the bone, where it perpetuates the vicious cycle leading to osteolytic lesions. This occurs when secreted factors from breast cancer cells disrupt bone homeostasis by deregulation of osteoblast bone formation, and enhance osteoclast bone degradation thereby releasing bone matrix bound growth factors leading to further tumor growth. Although the use of osteoclast targeting agents, such as bisphosphonates and RANK-L inhibitors, are common practice for the treatment of bone metastasis, they have not been shown to increase patient survival. We therefore sought to investigate the role of focal adhesion kinase (FAK), a potential therapeutic target, in the treatment of breast cancer mediated osteolysis. FAK is a non-receptor tyrosine kinase known to directly regulate tumor progression and metastasis; it is also expressed in all of the cell types involved in breast cancer mediated osteolysis. Thus, we hypothesized that the inhibition of FAK would restore normal bone homeostasis, as well as mediate direct anti-tumor activity. FAK depletion resulted in the decrease of expression of several osteolytic factors secreted by breast cancer cells. However, the use of FAK depleted breast cancer conditioned media did not prevent breast cancer mediated osteoclastogenesis in an osteoblast/osteoclast coculture. In monoculture however, using the FAK inhibitor PF-271, we have shown that FAK inhibition leads to increased apoptosis of mature osteoclasts, and their decreased ability to degrade mineralized bone matrix, perhaps in part due to reduced expression of lytic factors such as tartrate resistant acid phosphatase and cathepsin K. Further, FAK inhibition in osteoblast monoculture led to a decrease in their ability to express the maturation factor alkaline phosphatase, and also inhibited their ability to induce mineralization. This inhibition may be due in part to the specific effects of FAK inhibition using PF-271, which may result in decreased levels of p53 in treated osteoblasts. These results suggests that the pharmacological inhibition of FAK can effect all three cell types involved in the vicious cycle of bone metastasis, and as such could be a beneficial therapeutic for patients with bone metastasis resulting in prevention of bone degradation along with direct inhibition of tumor growth. However, it may require further evaluation in animal models to determine if observed effects on osteoblast activity in vitro also occurs in vivo with possible detrimental effects on restoration of damaged bone.

Wear particle-induced inflammation leading to periprosthetic osteolysis remains a major cause of hip implant failure. As polyethylene particles from conventional metal-on-polyethylene implants have been associated with these failures, an interest in lower wear metal-on-metal (MM) bearings has emerged. However, the biological effects of nanometer-size chromium oxide particles, predominant type of wear particles produced by MM implants, remain mostly unknown. Therefore, this study aimed to determine the cytotoxicity of nanometer-size Cr2O3 particles on macrophages in vitro, by analyzing their effects on cell mortality and cytokine release and comparing them with those of similarly-sized alumina (Al2O3) particles (known to be relatively bioinert). Results showed that at high concentrations, nanometer-size Cr2O3 particles can be cytotoxic to macrophages, inducing significant decreases in total cell numbers and increases in necrosis. Results also showed that, at high concentrations, the cytotoxicity of Cr2O3 particles was overall higher than that of Al2O3 particles, even though Cr2O3 and Al2O3 are both stable forms of ceramic materials. However, it appeared to be lower than that of previously reported conventional polyethylene and CoCrMo particles. Therefore, chromium oxide particles may not be the main culprit in initiating the inflammatory reaction in MM periprosthetic tissues.

Wear particle-induced inflammation leading to periprosthetic osteolysis remains a major cause of hip implant failure. As polyethylene particles from conventional metal-on-polyethylene implants have been associated with these failures, an interest in lower wear metal-on-metal (MM) bearings has emerged. However, the biological effects of nanometer-size chromium oxide particles, predominant type of wear particles produced by MM implants, remain mostly unknown. Therefore, this study aimed to determine the cytotoxicity of nanometer-size Cr2O3 particles on macrophages in vitro, by analyzing their effects on cell mortality and cytokine release and comparing them with those of similarly-sized alumina (Al2O3) particles (known to be relatively bioinert). Results showed that at high concentrations, nanometer-size Cr2O3 particles can be cytotoxic to macrophages, inducing significant decreases in total cell numbers and increases in necrosis. Results also showed that, at high concentrations, the cytotoxicity of Cr2O3 particles was overall higher than that of Al2O3 particles, even though Cr2O3 and Al2O3 are both stable forms of ceramic materials. However, it appeared to be lower than that of previously reported conventional polyethylene and CoCrMo particles. Therefore, chromium oxide particles may not be the main culprit in initiating the inflammatory reaction in MM periprosthetic tissues.

Wear particle-induced inflammation leading to periprosthetic osteolysis remains a major cause of hip implant failure. As polyethylene particles from conventional metal-on-polyethylene implants have been associated with these failures, an interest in lower wear metal-on-metal (MM) bearings has emerged. However, the biological effects of nanometer-size chromium oxide particles, predominant type of wear particles produced by MM implants, remain mostly unknown. Therefore, this study aimed to determine the cytotoxicity of nanometer-size Cr2O3 particles on macrophages in vitro, by analyzing their effects on cell mortality and cytokine release and comparing them with those of similarly-sized alumina (Al2O3) particles (known to be relatively bioinert). Results showed that at high concentrations, nanometer-size Cr2O3 particles can be cytotoxic to macrophages, inducing significant decreases in total cell numbers and increases in necrosis. Results also showed that, at high concentrations, the cytotoxicity of Cr2O3 particles was overall higher than that of Al2O3 particles, even though Cr2O3 and Al2O3 are both stable forms of ceramic materials. However, it appeared to be lower than that of previously reported conventional polyethylene and CoCrMo particles. Therefore, chromium oxide particles may not be the main culprit in initiating the inflammatory reaction in MM periprosthetic tissues.

Wear particle-induced inflammation leading to periprosthetic osteolysis remains a major cause of hip implant failure. As polyethylene particles from conventional metal-on-polyethylene implants have been associated with these failures, an interest in lower wear metal-on-metal (MM) bearings has emerged. However, the biological effects of nanometer-size chromium oxide particles, predominant type of wear particles produced by MM implants, remain mostly unknown. Therefore, this study aimed to determine the cytotoxicity of nanometer-size Cr2O3 particles on macrophages in vitro, by analyzing their effects on cell mortality and cytokine release and comparing them with those of similarly-sized alumina (Al2O3) particles (known to be relatively bioinert). Results showed that at high concentrations, nanometer-size Cr2O3 particles can be cytotoxic to macrophages, inducing significant decreases in total cell numbers and increases in necrosis. Results also showed that, at high concentrations, the cytotoxicity of Cr2O3 particles was overall higher than that of Al2O3 particles, even though Cr2O3 and Al2O3 are both stable forms of ceramic materials. However, it appeared to be lower than that of previously reported conventional polyethylene and CoCrMo particles. Therefore, chromium oxide particles may not be the main culprit in initiating the inflammatory reaction in MM periprosthetic tissues.

Gorham-Stout syndrome is an extremely rare pathology, of unknown etiology. It is characterized by proliferation of vascular channels that causes destruction and reabsorption of the bone matrix. We present a nine year-old male patient with an acute episode characterized by fever, chest pain, respiratory distress and dyspnea. The patient was submitted to computed tomography scan and a biopsy. The findings in the biopsy were multiple lytic lesions, osteolysis, and a mediastinal lymphangioma (lymphangiomatosis). The diagnosis was Gorham-Stout syndrome with atypical presentation. / jorgeluisnp@gmail.com / El síndrome de Gorham-Stout es una patología ósea extremadamente rara de etiología desconocida, caracterizada histopatológicamente por proliferación de los canales vasculares, que origina destrucción y resorción de la matriz ósea. Se presenta el caso de un paciente varón de nueve años de edad con un cuadro agudo caracterizado por fiebre, dolor torácico, dificultad respiratoria y disnea ante pequeños esfuerzos. Se realizaron estudios de imágenes y patología, en los que se encontraron lesiones liticas múltiples y presencia de un linfangioma mediastínico. Se diagnosticó síndrome de Gorham-Stout. Esta es una presentación atípica debido a la localización de la linfangiomatosis y al tamaño de la masa.