Corrigendum to "Mikkeli Osteoporosis Index Identifies Fracture Risk Factors and Osteoporosis and Intervention Thresholds Parallel with FRAX".

[This corrects the article DOI: 10.4061/2011/732560.].

Atlas-based knee osteophyte assessment with ultrasonography and radiography: relationship to arthroscopic degeneration of articular cartilage.

OBJECTIVES: To investigate intra- and inter-reader agreement of ultrasonography (US) and conventional radiography (CR) for the evaluation of osteophyte presence and size within the tibiofemoral joint. In addition, to correlate these findings with arthroscopic degeneration of the articular cartilage. METHOD: Forty adult patients with knee pain were enrolled in this study. Knee CR and US scanning of the medial and lateral bone margins were performed on all patients. A novel atlas for the US grading of knee osteophytes was used in the evaluation. The number and size of the osteophytes were evaluated semi-quantitatively in two rounds from both the CR images (four readers) and the US images (14 readers). The Noyes grading system was used for the evaluation of arthroscopic degeneration of the articular cartilage in 26 patients. RESULTS: On average, intra- and inter-reader US and CR agreement was substantial and comparable to each other (κ = 0.60-0.72). US detected more osteophytes than CR at both the medial (65% vs. 48%) and lateral (70% vs. 60%) compartments. A statistically significant correlation between CR- or US-based osteophyte and arthroscopy grades was observed only for US at the medial compartment (rs = 0.747, p < 0.001). CONCLUSIONS: The detection of knee osteophytes using the novel US atlas is as reproducible as reading conventional radiographs. US is more sensitive to detect knee osteophytes than CR. Furthermore, osteophytes detected with US correlate significantly with arthroscopic cartilage changes at the medial knee compartment whereas those detected by CR do not.

Diagnostic performance of knee ultrasonography for detecting degenerative changes of articular cartilage.

OBJECTIVE: To investigate the diagnostic performance of non-invasive knee ultrasonography (US) to detect degenerative changes of articular cartilage using arthroscopic grading as the gold standard. DESIGN: Forty adult patients referred to a knee arthroscopy because of knee pain were randomly selected for the study. Before the arthroscopy, knee US was performed and cartilage surfaces at medial and lateral femoral condyles as well as at intercondylar notch area (sulcus) were semi-quantitatively graded from US. Ultrasonographic grading was compared with the arthroscopic Noyes' grading for cartilage degeneration. RESULTS: Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic odds ratio for detecting arthroscopic cartilage changes in US varied between 52 and 83%, 50-100%, 88-100%, 24-46%, and 5.0-13.0, respectively, depending on the site. Correlation of severity of cartilage changes (grades) between US and arthroscopy varied from insignificant to significant depending on the site: at the sulcus area the correlation was highest (r(s)=0.593, P<0.001), at the medial condyle also significant (r(s)=0.465, P=0.003), and at the lateral condyle non-significant (r(s)=0.262, P=0.103). The sum of cartilage grades in all three sites of the femoral cartilage between US and arthroscopy had the highest correlation (r(s)=0.655, P<0.001). CONCLUSIONS: Positive finding in US is a strong indicator of arthroscopic degenerative changes of cartilage, but negative finding does not rule out degenerative changes. Non-invasive knee US is a promising technique for screening of degenerative changes of articular cartilage, e.g., during osteoarthritis.

Mikkeli Osteoporosis Index Identifies Fracture Risk Factors and Osteoporosis and Intervention Thresholds Parallel with FRAX.

Osteoporosis Index (MOI) was developed from Fracture Index (FI), a validated fracture risk score, to identify also osteoporosis. MOI risk factors are age, weight, previous fracture, family history of hip fracture or spinal osteoporosis, smoking, shortening of the stature, and use of arms to rise from a chair. The association of these risk factors with BMD was examined in development cohorts of 300 Finnish postmenopausal women with a fracture and in a population control of 434 women aged 65-72. Validation cohorts included 200 fracture patients and a population control of 943 women aged 58-69. MOI identified femoral neck osteoporosis in these cohorts as well as the Osteoporosis Self-Assessment Tool (OST). In the pooled fracture cohort, the association of BMI-based FRAX fracture risk with MOI was good. After BMD measurement, MOI identified well FRAX hip fracture risk-based Intervention Thresholds (ITs) (AUC 0.74-0.90).

Insulin-like growth factors I and II in the aseptic loosening of total hip implants.

Periprosthetic interface tissue and pseudocapsule samples surrounding aseptically loosened hip implants and control knee synovium were studied by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Endothelial cells, fibroblasts, and monocyte/macrophages contained bone formation-enhancing insulin-like growth factors (IGFs). In interface tissue we found fewer IGF-I and IGF-II positive cells than in control tissue. In pseudocapsular tissue we found fewer IGF-I positive cells and an equal amount of IGF-II positive cells compared to control tissues. Decreased bone formation may contribute to net loss of bone around aseptically loosened hip implants.

Removal of hyaline articular cartilage reduces lymphocyte infiltration and activation in rheumatoid synovial membrane.

OBJECTIVE: To analyze the effect of removal of hyaline articular cartilage on synovial membrane pathology in chronic arthritis. METHODS: Synovial membrane samples were obtained from patients with rheumatoid arthritis or ankylosing spondylitis in association with total hip arthroplasty, either primary or revision surgery. Synovial membrane histopathology was assessed by immunochemical staining and morphometry. RESULTS: CD68 positive macrophages were common in revision synovial membranes. In contrast, T lymphocytes were much more common in primary rheumatoid synovial membranes (p < 0.001). Many T lymphocytes in primary synovial membrane were HLA-D/DR positive (p < 0.001) and interleukin 2 receptor (IL-2R) positive (p < 0.001) and contained interferon-gamma(IFN-gamma; p < 0.001) and tumor necrosis factor-beta (TNF-beta; p < 0.001). In contrast, revision synovial membranes from patients with chronic arthritis contained only a few HLA-D/DR positive T cells and practically no IL-2R, IFN-gamma, or TNF-beta positive activated T lymphocytes. CONCLUSION: The components of hyaline articular cartilage may be the source of autoantigen responsible for perpetuation of chronic arthritides.

No lymphokines in T-cells around loosened hip prostheses.

Research results have been contradictory about the role of lymphocytes and immune response in aseptic loosening of total hip replacement (THR). Conclusive evidence is still lacking in spite of extensive in vivo and in vitro studies. Our study was designed to check whether T-cells were activated and if they produced lymphokines in synovial membrane-like interface tissue around loosened THRs. Tissue sections were stabilized and permeabilized to allow the cytokine-specific antibodies to penetrate through the cell membrane and the membranes of intracellular organelles. This technique, combined with computer-assisted image analysis, permits the detection and quantitation of lymphokine-producing cells. We found that the number of T-cells was low, and none of the T-cells was activated, as shown by the absence of interleukin-2 receptor (IL-2R) immunoreactivity. There was no cell producing lymphokines, such as interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and tumor necrosis factor-beta (TNF-beta). Our results suggest that T-cell-mediated immune response is not actively involved in aseptic loosening of THR.

Increased interleukin-8 (IL-8) expression is related to aseptic loosening of total hip replacement.

Aseptic loosening is an increasing problem in total hip replacement (THR). Chronic inflammatory reaction against implant wear particle results in collageno- and osteolysis, leading to loosening of the implant. Cytokines are known to play a major role in this particular inflammatory process. The aim of the present study was to examine interleukin-8 (IL-8) in the synovial-like interface membrane (SLIM) and pseudocapsular tissue of THRs and to compare it to normal knee synovial membrane. Eleven patients suffering from aseptically loosened THRs were included. All the SLIM and pseudocapsular tissue samples were obtained during revision operations. Ten control samples of normal synovium were collected per arthroscopy from the superior recessus of the knee. For immunohistochemical IL-8 detection, polyclonal mouse anti-human immunoglobulin (Ig)G1 IL-8-primary antibody was used with the alkaline phosphatase anti-alkaline phosphatase (APAAP) method. Results were quantitated using the Vidas image analysis system. The highest count levels (mean +/- SEM) were detected in SLIM tissue (386+/-82 cells/mm2). The difference was statistically significant compared with pseudocapsular tissue (193+/-36 cells/mm2) and control samples (18+/-5 cells/mm2). Count levels in control tissue were on average 5% of the SLIM tissues values. The present study determines for the first time the cellular origin of IL-8 in aseptically loosened THRs and also quantitates the IL-8-producing cells in the periprosthetic tissue. The results reveal a high rise in IL-8 concentration in SLIM and in synovial tissues. This finding moves us one step forward in solving the complex network of multiple factors affecting loosening of hip implants.

Production of platelet-derived growth factor in aseptic loosening of total hip replacement.

Aseptic loosening is the predominant cause of total hip implant failure. It has been assumed that a layer or membrane, containing macrophages, fibroblasts and vascular endothelial cells, of synovial-like tissue develops at the implant-to-bone interface almost invariably and, with time, somehow leads to loosening of the components from the surrounding bone. These cells produce a variety of cytokines and proteolytic enzymes which stimulate bone resorption. Platelet derived growth factor (PDGF) may be one of the cytokines which stimulate bone resorption and contribute to aseptic loosening in total hip replacement (THR). Synovial-like membrane from the implant or cement-to-bone interface (n = 10) and pseudocapsule (n = 10) were obtained from ten patients operated on for aseptic loosening of THR. As a control, nine samples of connective tissues were obtained from patients who had mandibular or maxillary fractures fixed with bone implant. The avidin-biotin-peroxidase complex (ABC) method with polyclonal rabbit anti-human IgG against the A-chain and B-chain of PDGF was used for staining. ABC-alkaline phosphatase-anti-alkaline-phosphatase double staining with monoclonal mouse anti-human fibroblast IgG1 and CD68 antibodies was used to ascertain the cellular origin of PDGF. Results of the PDGF staining were quantitated by a semi-automatic VIDAS image analysis system. The PDGF-A and PDGF-B chain containing cells were found in all periprosthetic tissues, in particular in macrophages with phagocytosed particulate debris, but to some extent also in fibroblasts and in endothelial cells. The numbers of PDGF-A and PDGF-B chain positive cells per mm 2 in synovial-like interface membrane (1881 +/- 486 and 1877 +/- 214) and pseudocapsule (1786 +/- 236 and 1676 +/- 152) were higher (P < 0.01) around loose THR than in control tissue (821 +/- 112 and 467 +/- 150), respectively. The results of the present study suggest that PDGF is preferably expressed by macrophages, which to an increased extent produce it in the synovial-like interface membrane and pseudocapsular synovial-like membrane. Because of its role in bone resorption, it may well play a role in periprosthetic bone loss and aseptic loosening and deserves more detailed study as a mediator and potential target in the modulation or prevention of loosening of THR.

Macrophage-colony stimulating factor (M-CSF) is increased in the synovial-like membrane of the periprosthetic tissues in the aseptic loosening of total hip replacement (THR).

The aim of the study was to assess the eventual presence, cellular localization and extent of expression of the osteoclast activating cytokine M-CSF (CSF-1) in the periprosthetic tissues around loose total hip replacement (THR). Synovial-like membrane was obtained from the implant-to-bone interface and pseudocapsule from ten total hip revisions performed for aseptic loosening and compared to ten hip synovial tissue samples obtained from ten patients who had primary THR for osteoarthritis. Avidin-biotinperoxidase complex (ABC) and alkaline phosphatase-anti-alkaline phosphatase (APAAP) methods were used for staining and VIDAS image analysis for quantification. M-CSF was mainly produced by macrophages, which often contained wear particles, but also by some fibroblasts and vascular endothelial cells. The number of cells containing (per one mm2 tissue) clearly increased in the interface (1585 +/- 212; p < 0.01) and pseudocapsular (1456 +/- 248; p < 0.01) tissue compared to synovial tissue (543 +/- 118). The present findings suggest, that inflammatory foreign-body type of response enhances expression of M-CSF in cases of aseptic loosening of THR. M-CSF produced in the synovial-like membrane in the implant-bone interface may contribute to activation of osteoclasts in periprosthetic bone and thus to loosening.

Transforming growth factor-beta 1 and 2 in the synovial-like interface membrane between implant and bone in loosening of total hip arthroplasty.

OBJECTIVE: Development of a synovial-like membrane in the implant-bone or cement-bone interface has been linked to aseptic loosening of total hip arthroplasties (THA). This tissue consists of a fibrous stroma containing blood vessels and macrophages, but with relatively few lymphocytes, compared to "autoimmune" rheumatoid synovitis. Our aim was to examine transforming growth factor-beta (TGF-beta) in the synovial-like membrane of the interface and pseudocapsular tissue of loose THA and compare it to control knee synovial membrane. METHODS: Twenty samples obtained from 10 patients with loose THA at revisions performed for aseptic loosening and 10 samples of knee synovial membrane as controls were analyzed for TGF-beta expression using rabbit antihuman TGF-beta 1 and TGF-beta 2 IgG in immunohistochemical staining. Results were quantitated by a semi-automatic VIDAS image analysis system. RESULTS: Immunoperoxidase staining disclosed TGF-beta in macrophages and fibroblasts and also in some vascular endothelial cells and in occasional lymphocytes. Image analysis showed an increased number of positive cells/mm2 of both TGF-beta 1 (2327 +/- 212 vs 946 +/- 136; p < 0.01) and TGF-beta 2 (2292 +/- 594 vs 311 +/- 113; p < 0.01) compared to the control tissue. Increased expression of both TGF-beta 1 and TGF-beta 2 was also shown in the pseudocapsule (3210 +/- 585 and 1796 +/- 214). Use of cement or type of alloy did not seem to have any great effect on local expression of TGF-beta. CONCLUSION: Profibrotic and immunosuppressive TGF-beta are increased in the synovial-like membrane in periprosthetic tissues around loose hip prostheses. They may play a role in the formation, maintenance, and growth of the interface tissue, and thus in the aseptic loosening of THA.

Basic fibroblast growth factor (bFGF) in the synovial-like membrane around loose total hip prostheses.

The aim of this investigation was to examine the eventual presence of bFGF in the synovial-like membrane of the interface and pseudocapsular tissue of loose total hip replacement (THR) and compare it to control knee synovial membrane. bFGF was demonstrated using specific antibodies in avidin-biotin-peroxidase complex (ABC) staining and quantitated using a semiautomatic VIDAS image analysis system. bFGF was found in fibroblasts, in vascular endothelial cells and in particular in macrophages in a characteristic pattern. The number of bFGF positive cells per one mm2 was increased in interface (1693 +/- 291; n = 10; p < 0.01) and pseudocapsular tissue (1954 +/- 256; n = 10; p < 0.01), compared to the knee joint synovial membrane (1009 +/- 133; n = 10). These findings suggest that bFGF is involved in the enhanced tissue remodelling of the synovial-like membrane around loose total hip prostheses. Codistribution of metallosis and bFGF positive macrophages suggests a chronic foreign body type reaction as the driving stimulus.