Predicting bone loss following orthotopic liver transplantation.
BACKGROUND: Hepatic osteodystrophy occurs in the majority of patients with advanced chronic liver disease with the abnormalities in bone metabolism accelerating following orthotopic liver transplantation (OLT). AIMS: To examine changes in bone mineral density (BMD) following OLT and to investigate factors that lead to bone loss. METHODS: Twelve patients had BMD (at both the lumbar spine (LS) and femoral neck (FN)) and biochemical markers measured preoperatively and for 24 months following OLT. RESULTS: BMD was low in 75% of patients prior to OLT and decreased significantly from baseline at the LS at three months and the FN at six months. BMD began to increase thereafter at both sites, approaching baseline values at the LS by 12 months. Bone formation markers, osteocalcin and procollagen type I carboxy propeptide, decreased immediately post-OLT, with a concomitant increase seen in the resorption markers pyridinoline and deoxypyridinoline. This resulted in a negative uncoupling index early post-OLT, that rebounded to positive values after six months. There was a significant correlation between the change in the uncoupling index between six and three months which preceded the increase in BMD at 12 months. The decrease in BMD recorded early post-OLT correlated with vitamin D levels at three months. CONCLUSIONS: Results suggest that increased resorption and inadequate formation are the major contributors to additional bone loss following OLT. Non-invasive biochemical markers precede later changes in BMD in this patient group following OLT and may have a role in investigating and planning intervention strategies to prevent bone loss in future studies. (+info)
Analysis of 118 second-generation metal-on-metal retrieved hip implants.
Osteolysis is due to particulate wear debris and is responsible for the long-term failure of total hip replacements. It has stimulated the development of alternative joint surfaces such as metal-on-metal or ceramic-on-ceramic implants. Since 1988 the second-generation metal-on-metal implant Metasul has been used in over 60 000 hips. Analysis of 118 retrieved specimens of the head or cup showed rates of wear of approximately 25 microm for the whole articulation per year in the first year, decreasing to about 5 microm per year after the third. Metal surfaces have a 'self-polishing' capacity. Scratches are worn out by further joint movement. Volumetric wear was decreased some 60-fold compared with that of metal-on-polyethylene implants, suggesting that second-generation metal-on-metal prostheses may considerably reduce osteolysis. (+info)
Induction of macrophage C-C chemokine expression by titanium alloy and bone cement particles.
Particulate wear debris is associated with periprosthetic inflammation and loosening in total joint arthroplasty. We tested the effects of titanium alloy (Ti-alloy) and PMMA particles on monocyte/macrophage expression of the C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), monocyte inflammatory protein-1 alpha (MIP-1alpha), and regulated upon activation normal T expressed and secreted protein (RANTES). Periprosthetic granulomatous tissue was analysed for expression of macrophage chemokines by immunohistochemistry. Chemokine expression in human monocytes/macrophages exposed to Ti-alloy and PMMA particles in vitro was determined by RT-PCR, ELISA and monocyte migration. We observed MCP-1 and MIP-1alpha expression in all tissue samples from failed arthroplasties. Ti-alloy and PMMA particles increased expression of MCP-1 and MIP-1alpha in macrophages in vitro in a dose- and time-dependent manner whereas RANTES was not detected. mRNA signal levels for MCP-1 and MIP-1alpha were also observed in cells after exposure to particles. Monocyte migration was stimulated by culture medium collected from macrophages exposed to Ti-alloy and PMMA particles. Antibodies to MCP-1 and MIP-1alpha inhibited chemotactic activity of the culture medium samples. Release of C-C chemokines by macrophages in response to wear particles may contribute to chronic inflammation at the bone-implant interface in total joint arthroplasty. (+info)
Treatment of multiple myeloma.
BACKGROUND AND OBJECTIVE: Multiple myeloma (MM) accounts for about 10% of all hematologic malignancies. The standard treatment with intermittent courses of melphalan and prednisone (MP) was introduced more than 30 years ago and, since then there has been little improvement in event-free and overall survival (EFS & OS). The aim of this article is to review: 1) the role of initial chemotherapy (ChT), maintenance treatment with alpha-interferon and salvage ChT, 2) the results of high-dose therapy (HDT) followed by allogeneic or autologous stem cell transplantation (allo-SCT and auto-SCT), and 3) the most important supportive measures. EVIDENCE AND INFORMATION SOURCES: The authors of this review have been actively working and contributing with original investigations on the treatment of MM during the last 15 years. In addition, the most relevant articles and recent abstracts published in journals covered by the Science Citation Index and Medline are also reviewed. STATE OF THE ART AND PERSPECTIVES: The importance of avoiding ChT in asymptomatic patients (smoldering MM) is emphasized. The criteria and patterns of response are reviewed. MP is still the standard initial ChT with a response rate of 50-60% and an OS of 2-3 years. Combination ChT usually increases the response rate but does not significantly influence survival when compared with MP. Exposure to melphalan should be avoided in patients in whom HDT followed by auto-SCT is planned, in order to not preclude the stem cell collection. The median response duration to initial ChT is 18 months. Interferon maintenance usually prolongs response duration but in most studies does not significantly influence survival (a large meta-analysis by the Myeloma Trialists' Collaborative Group in Oxford is being finished). In alkylating-resistant patients, the best rescue regimens are VBAD or VAD. In patients already resistant to VBAD or VAD and in those in whom these treatments are not feasible we recommend a conservative approach with alternate day prednisone and pulse cyclophosphamide. While HDT followed by autotransplantation is not recommended for patients with resistant relapse, patients with primary refractory disease seem to benefit from early myeloablative therapy. Although results from large randomized trials are still pending in order to establish whether early HDT intensification followed by auto-SCT is superior to continuing standard ChT in responding patients, the favorable experience with autotransplantation of the French Myeloma Intergroup supports this approach. However, although the complete response rate is higher with intensive therapy, the median duration of response is relatively short (median, 16 to 36 months), with no survival plateau. There are several ongoing trials comparing conventional ChT with HDT/autoSCT in order to identify the patients who are likely to benefit from one or another approach. With allo-SCT there is a transplant-related mortality ranging from 30 to 50% and also a high relapse rate in patients achieving CR. However, 10 to 20% of patients undergoing allo-SCT are long-term survivors (> 5 years) with no evidence of disease and, consequently, probably cured. The use of allogeneic peripheral blood stem cells (PBSC) in order to speed the engraftment and also the use of partially T-cell depleted PBSC which can decrease the incidence of graft-versus-host disease are promising approaches. In the setting of allo-SCT, donor lymphocyte infusion is an encouraging strategy in order to treat or prevent relapses. Finally, important supportive measures such as the treatment of anemia with erythropoietin, the management of renal failure and the use of bisphosphonates are reviewed. (+info)
Massive pelvic and femoral pseudotumoral osteolysis secondary to an uncemented total hip arthroplasty.
A 51 year-old man developed an extensive osteolytic response to wear debris in an uncemented porous-coated total hip arthroplasty, with metal/polyethylene interface, which had been implanted eighteen years previously. This reaction, which involved the upper femur and the ilium, produced a mass which compressed the pelvic viscera. (+info)
Improving the detection of acetabular osteolysis using oblique radiographs.
Visualisation of periacetabular osteolysis by standard anteroposterior (AP) radiographs underestimates the extent of bone loss around a metal-backed acetabular component. We have assessed the effectiveness of standard radiological views in depicting periacetabular osteolysis, and recommend additional projections which make these lesions more visible. This was accomplished using a computerised simulation of radiological views and a radiological analysis of simulated defects placed at regular intervals around the perimeter of a cadaver acetabulum. The AP view alone showed only 38% of the defects over all of the surface of the cup and failed to depict a 3 mm lesion over 83% of the cup. When combined with the AP view, additional 45 degree obturator-oblique and iliac-oblique projections increased the depiction, showing 81% of the defects. The addition of the 60 degree obturator-oblique view further improved the visualisation of posterior defects, increasing the rate of detection to 94%. Based on this analysis, we recommend using at least three radiographic views when assessing the presence and extent of acetabular osteolysis. (+info)
Polyethylene wear, osteolysis and acetabular loosening with an HA-coated hip prosthesis. A follow-up of 94 consecutive arthroplasties.
We have followed up for a period of seven to nine years 100 consecutive arthroplasties of the hip in which an entirely HA-coated implant had been used. The clinical results were excellent and bony incorporation was extensive in all components. No stem became loose or subsided but five cups were revised because of loosening after 3.8 to 5.5 years, having functioned painlessly and shown radiological ingrowth. Revision procedures because of excessive polyethylene wear have been performed on 18 hips and are planned for six more. Two eroded metal backings with worn-through polyethylene were exchanged; six hips showed metallosis without polyethylene wear-through. There were two cases of granulomatous cysts in the groin and 66 hips had osteolysis located periarticularly, in the greater trochanter or in the acetabulum. (+info)
Multiple osteolysis of peripheral extremities in a patient with adult T cell leukemia/lymphoma.
A 67-year-old woman with severe pain in the peripheral extremities was admitted to our hospital. Radiography of the peripheral extremities revealed multiple osteolytic lesions. Antibody to human T cell leukemia virus type-I (HTLV-I) was positive, and right radial bone biopsy showed infiltration of adult T cell leukemic (ATL) cells. Irradiation therapy was effective in the osteolytic lesions. In the present case, elevation of IL-6 was detected, suggesting that IL-6 produced by ATL cells is related to their proliferation in the bone, and local osteolysis. (+info)