Martin Fuerst

Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis

Aggrecan cleavage by a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 5 (ADAMTS-5) is crucial for the breakdown of cartilage matrix during osteoarthritis, a degenerative joint disease that leads to the progressive destruction of articular structures. The mechanisms of ADAMTS-5 activation and their links to the pathogenesis of osteoarthritis remain poorly understood, but syndecans have been shown to be involved in the activation of ADAMTS-4 (ref. 3). Here we show that syndecan-4 is specifically induced in type X collagen–producing chondrocytes both in human osteoarthritis and in murine models of the disease. The loss of syndecan-4 in genetically modified mice and intra-articular injections of syndecan-4–specific antibodies into wild-type mice protect from proteoglycan loss and thereby prevent osteoarthritic cartilage damage in a surgically induced model of osteoarthritis. The occurrence of less severe osteoarthritis-like cartilage destruction in both syndecan-4–deficient mice and syndecan-4–specific antibody–treated wild-type mice results from a marked decrease in ADAMTS-5 activity. Syndecan-4 controls the activation of ADAMTS-5 through direct interaction with the protease and through regulating mitogen-activated protein kinase (MAPK)-dependent synthesis of matrix metalloproteinase-3 (MMP-3). Our data suggest that strategies aimed at the inhibition of syndecan-4 will be of great value for the treatment of cartilage damage in osteoarthritis.

Calcification of articular cartilage in human osteoarthritis

OBJECTIVE Hypertrophic chondrocyte differentiation is a key step in endochondral ossification that produces basic calcium phosphates (BCPs). Although chondrocyte hypertrophy has been associated with osteoarthritis (OA), chondrocalcinosis has been considered an irregular event and linked mainly to calcium pyrophosphate dihydrate (CPPD) deposition. The aim of this study was to determine the prevalence and composition of calcium crystals in human OA and analyze their relationship to disease severity and markers of chondrocyte hypertrophy. METHODS One hundred twenty patients with end-stage OA undergoing total knee replacement were prospectively evaluated. Cartilage calcification was studied by conventional x-ray radiography, digital-contact radiography (DCR), field-emission scanning electron microscopy (FE-SEM), and synovial fluid analysis. Cartilage calcification findings were correlated with scores of knee function as well as histologic changes and chondrocyte hypertrophy as analyzed in vitro. RESULTS DCR revealed mineralization in all cartilage specimens. Its extent correlated significantly with the Hospital for Special Surgery knee score but not with age. FE-SEM analysis showed that BCPs, rather than CPPD, were the prominent minerals. On histologic analysis, it was observed that mineralization correlated with the expression of type X collagen, a marker of chondrocyte hypertrophy. Moreover, there was a strong correlation between the extent of mineralization in vivo and the ability of chondrocytes to produce BCPs in vitro. The induction of hypertrophy in healthy human chondrocytes resulted in a prominent mineralization of the extracellular matrix. CONCLUSION These results indicate that mineralization of articular cartilage by BCP is an indissociable process of OA and does not characterize a specific subset of the disease, which has important consequences in the development of therapeutic strategies for patients with OA.

The value of synovial biopsy, joint aspiration and C-reactive protein in the diagnosis of late peri-prosthetic infection of total knee replacements

We analysed the serum C-reactive protein level, synovial fluid obtained by joint aspiration and five synovial biopsies from 145 knee replacements prior to revision to assess the value of these parameters in diagnosing late peri-prosthetic infection. Five further synovial biopsies were used for histological analysis. Samples were also obtained during the revision and incubated and analysed in an identical manner for 14 days. A total of 40 total knee replacements were found to be infected (prevalence 27.6%). The aspiration technique had a sensitivity of 72.5% (95% confidence interval (CI) 58.7 to 86.3), a specificity of 95.2% (95% CI 91.2 to 99.2), a positive predictive value of 85.3% (95% CI 73.4 to 100), a negative predictive value of 90.1% (95% CI 84.5 to 95.7) and an accuracy of 89%. The biopsy technique had a sensitivity of 100%, a specificity of 98.1% (95% CI 95.5 to 100), a positive predictive value of 95.2% (95% CI 88.8 to 100), a negative predictive value of 100% and an accuracy of 98.6%. C-reactive protein with a cut-off-point of 13.5 mg/l had a sensitivity of 72.5% (95% CI 58.7 to 86.3), a specificity of 80.9% (95% CI 73.4 to 88.4), a positive predictive value of 59.2% (95% CI 45.4 to 73.0), a negative predictive value of 88.5% (95% 81.0 to 96.0 CI) and an accuracy of 78.1%. We found that biopsy was superior to joint aspiration and C-reactive protein in the diagnosis of late peri-prosthetic infection of total knee replacements.

Periprosthetic fractures of the femur associated with hip arthroplasty

The nature of the treatment of periprosthetic fractures depends on the localisation, the stability of the prosthesis and the condition of the bone. The Vancouver fracture classification has proved to be of value in determining specific modes of treatment. The current review analyses the different therapeutic options resulting in a concept of fracture-specific treatment. In this report we propose an extended version of this classification in which periprosthetic fractures associated with endoprostheses anchored in the epiphysis or metaphysis, as well as interprosthetic fractures, are taken into consideration.

Investigation of calcium crystals in OA knees

For studies on matrix mineralization in osteoarthritis (OA), a clear analytical approach is necessary to identify and to quantify mineralization in the articular cartilage. The aim of this study is to develop an effective algorithm to quantify and to identify cartilage mineralization in the experimental setting. Four patients with OA of the knee undergoing total knee replacement and four control patients were included. Cartilage calcification was studied by digital contact radiography (DCR), field emission scanning electron microscopy (FE-SEM) X-ray element analysis and Raman spectroscopy (RS). DCR revealed mineralization in all OA cartilage specimens. No mineralization was observed in the control cartilage. Patient I showed rhomboid shaped crystals with a mean Ca:P molar ratio of 1.04 indicated the presence of calcium pyrophosphate dihydrate (CPPD) crystals, while Patients II, III and IV presented carbonate-substituted hydroxyapatite (HA). RS also showed the presence of CPPD crystals in Patient I while Patients II, III and IV revealed spectra confirming the presence of HA crystals. In the corresponding chondrocyte cell culture analyzed with SEM, the presence of CPPD crystals in the culture of Patient I and HA crystals in the culture of Patient II, III and IV was confirmed. No mineralization was found in the cell culture of the controls. The differentiation between BCP and CPPD crystals plays an important role, and the techniques presented here provide an accurate differentiation of these two types of crystals. For quantification of articular cartilage mineralization, DCR is a simple and accurate method.

The DUROM Cup Humeral Surface Replacement in Patients with Rheumatoid Arthritis

BACKGROUND Rheumatoid arthritis often leads to severe destruction of the glenohumeral joint, including synovitis and inflammation-induced alterations of the rotator cuff. Cup arthroplasty, or surface replacement of the shoulder, was introduced in the 1980s. The aim of this study was to evaluate the midterm results of the DUROM cup surface replacement for patients with rheumatoid arthritis affecting the glenohumeral joint. METHODS From 1997 to 2000, forty-two DUROM cup hemiprostheses were implanted in a cohort of thirty-five patients (forty-two shoulders), who were evaluated preoperatively and again at three, twelve, and more than sixty months postoperatively. Six patients (seven shoulders) were lost to follow-up. Thirty-five shoulders in twenty-nine patients (twenty-one women and eight men with an average age of 61.4 years) could be evaluated prospectively after an average follow-up period of 73.1 months. Patients were evaluated clinically with the use of the Constant score, and a detailed radiographic analysis was performed to determine the presence of endoprosthetic loosening, glenohumeral subluxation, and glenoid bone loss. RESULTS The mean Constant score for the thirty-five shoulders increased from 20.8 points preoperatively to 64.3 points at a mean of 73.1 months postoperatively. There were three revisions: one to replace an implant that was too large, another to treat glenoid erosion, and a third due to loosening of the implant. No additional cases of loosening of the prosthesis or changes in cup position were observed radiographically. Over the five-year follow-up period, proximal migration of the cup increased in 63% of the shoulders, and glenoid depth increased in 31%. With the numbers studied, no differences in clinical outcome were identified between patients with a massive rotator cuff tear and those with a smaller or no tear. CONCLUSIONS The midterm results of the cemented DUROM cup surface replacement for patients with advanced rheumatoid arthritis of the shoulder are very encouraging, even for patients with a massive tear of the rotator cuff. The advantage of this cup arthroplasty is the less complex bone-sparing surgery. In the event of failure of the implant, other reliable salvage options remain available.

Distal Interlocking Screws With a Modular Revision Stem for Revision Total Hip Arthroplasty in Severe Bone Defects

A prospective study of 15 patients was designed to examine whether the modular cementless revision stem (Revitan curved; Zimmer GmbH, Winterthur, Switzerland) is suitable for stem revisions with a defective isthmus when distal interlocking screws are also used for fixation. During a follow-up period of 35.4 +/- 11.4 months (24-70 months), there was one stem loosening with screw breakage in a case of a stem that was too thin. According to Engh et al, bony ingrowth fixation of the stem occurred in 12 cases and stable fibrous fixation in 2 cases. The Harris Hip Score rose continuously from 44.7 +/- 12.9 points preoperatively to 75 +/- 10 points at 24 months. This concept of additional stem fixation with distal interlocking screws represents a useful treatment option for revision arthroplasty in rare cases of a defective isthmus.

Amyloid deposition in rheumatoid arthritis of the hip

The aim of this study was to examine the frequency of amyloid deposition in patients with end-stage rheumatoid arthritis (RA) of the hip. The impact on the clinical situation and the RA severity regarding the inflammation was analyzed. Fifty patients with RA who consecutively underwent total hip replacement were prospectively evaluated. X-rays of the patients were analyzed radiologically (Larsen score) to quantify the radiological changes. A clinical score (Harris Hip Score) was preoperatively calculated from every patient. A laboratory set of inflammation markers (erythrocyte sedimentation rate, CRP, serum amyloid A-SAA, electrophoresis) was measured in every patient the day before the operation. Specimens of bone and cartilage from the femoral head and of the capsule were obtained from every patient intraoperatively for histological evaluation. A histological grading was performed. In patients with amyloid deposits, the subtypes were characterized immunohistologically. Ninety-two percent of the patients had raised SAA in the blood samples, but the only amyloid subtype was ATTR. No correlation was found for any other measured item, such as inflammation signs in the blood samples, the histological grading, the radiological or the clinical score. Amyloid plays a role in inflammatory joint destruction processes in RA with raised SAA values, but the amyloid deposits in the joint are of a different subtype. Thus, these amyloid deposits can be considered as minor pathologic significance. A correlation to the radiological and histological changes was ruled out by our study. As in degenerative arthritis, ATTR amyloid deposits may be an incidental finding in aged joints.

Versagensursachen primärer Implantationen

Eine Analyse aller Endoprothesenregister und groser Huftendoprothetik-Studien [19, 26] zeigt, dass die Pfannenkomponente das Hauptproblem im Rahmen eines Implantatversagens darstellt. Die Pfanne fuhrt doppelt so haufig zu Problemen wie der Schaft.

Modulation of bovine chondrocyte metabolism by free periosteal grafts in vitro

Purpose Autologous chondrocyte transplantation (ACT) is an established method in cartilage repair. Although long-term results show durable repair of isolated cartilage defects, some problems still remain. Since hypertrophy of the transplanted periosteum is a common problem, alternatives for periosteum are in demand. Periosteal grafts have been reported to stimulate neochondrogenesis via paracrine effects. The objective of this study was to evaluate the modulation of chondrocyte metabolism by periosteal grafts in vitro. Methods Periosteal explants and articular chondrocytes obtained from slaughtered adult cattle were co-cultured in a newly established perfusion system. The experimental groups were: 1. monocultured chondrocytes; 2. chondrocytes cultured with synovial supernatants; 3. chondrocytes cultured with periosteal supernatants; 4. chondrocytes co-cultured with periosteal explants. Results Chondrocyte proliferation, evaluated by measuring total DNA content, was prolongated by periosteal and synovial explants. Immunocytochemical staining of collagen type II was stronger in monoculture than in co-culture. Protein biosynthetic activity estimated by [3H]-proline incorporation, as well as extracellular matrix deposition for collagen type II, were reduced by periosteal and synovial explants. Additionally, co-culturing led to a decrease in aggrecan synthesis and release. The inhibiting effects were significantly stronger when cellular chondrocyte-periosteal cross-talk was made possible via paracrine effects. Conclusions The results of our study suggest a catabolic effect of periosteal explants on isolated chondrocytes in vitro. Further investigations are necessary whether periosteum in ACT is dispensable.