Oliver Niggemeyer

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.

Ätiologie und Pathogenese der Osteochondrosis dissecans tali

ZusammenfassungDie Osteochondrosis dissecans tali stellt eine Sonderform der osteochondralen Läsionen des Talus (OLT) dar und sollte nosologisch von diesen unterschieden werden. Ein Trauma mit nachfolgend radiologisch gesicherter osteochondraler Defektzone wird als traumatische OLT der Osteochondrosis dissecans tali im engeren Sinne gegenübergestellt.Die Läsion stellt eine Erkrankung des subchondralen Knochens dar und kann nahezu alle Gelenke des menschlichen Körpers betreffen. Die OD des Talus ist nach Kniegelenk und Ellenbogen die dritthäufigste Lokalisation mit einem Anteil von 4% aller Fälle von OD. Bevorzugt tritt die Osteochondrosis dissecans tali im 2. Lebensjahrzehnt auf, wenngleich ein Auftreten in jeder Altersstufe prinzipiell möglich ist.Die unterschiedlichen ätiologischen Faktoren der Osteochondrosis dissecans (mechanich, vaskulär, endogen, genetisch, bakteriell-infektiös) sind auch für die Osteochondrosis dissecans tali diskutiert worden. Insgesamt wird das Trauma als wichtigster ätiopathogenetischer Mechanismus favorisiert. Unterschiedliche Arbeiten zeigen eine Koinzidenz mit Distorsions- und Supinationstraumata in der Anamnese. Die bevorzugte Lokalisation der Osteochondrosis dissecans tali im Bereich der medialen und seltener der lateralen Talusrolle deckt sich mit experimentellen Untersuchungen, die eine erhöhte mechanische Belastung der Areale bei Varus-/Valgushaltung bzw. Pro-/Supinationsstellung zeigen konnten.Das Supinationstrauma wird in der Modellvorstellung sowohl für die häufigere mediale tassenförmige Läsion (cup-shape) als auch für die laterale waffelförmige Läsion (waver-shape) verantwortlich gemacht. In Anbetracht der komplexen Biomechanik des oberen (OSG) und unteren Sprunggelenks (USG) stellen solche Vorstellungen eine unzulässige Vereinfachung dar, die in Zukunft weitergehender Abklärung bedarf.Die pathogenetischen Stadien unterscheiden sich bei der Osteochondrosis dissecans tali nicht von denen anderer Lokalisationen. Ist ein imaginärer Schwellenwert erreicht, kommt es im Initialstadium (Stadium I) zu einer subchondralen Osteonekrose, die bei ausbleibender Regeneration über eine subchondrale Sklerosierung (Stadium II) zu einer Demarkation (Stadium III) und schließlich zur Dissekation (Stadium IV) führen kann.Die klinische Symptomatik ist unspezifisch. Periartikuläre Schwellungen, Gelenkergüsse, Bewegungseinschränkungen und seltener Gelenkblockaden werden beklagt. Differentialdiagnostisch ist die Abgrenzung zwischen OLT und Osteochondrosis dissecans tali meist schwierig. Hingegen kann die Osteochondrosis dissecans tali von anderen Erkrankungen des Sprunggelenks (Talusnekrosen, Subchondrale Ganglien) gut unterschieden werden.AbstractOsteochondritis dissecans of the talus is a particular form of osteochondral lesions of the talus. A trauma with subsequent osteochondral defect detected immediately by radiology has to be differentiated from osteochondritis dissecans of the talus.Osteochondritis dissecans (o.d.) is primarily a disease of the subchondral bone and can affect almost every joint in the human organism. After the knee and elbow, the talus is the third most common site of the disease accounting for 4% of all cases. It mostly arises in the 2nd decade but can occur at almost any age.Different etiological factors of osteochondritis dissecans (vascular, traumatic, infectious, endogenous, genetic) are discussed in general and in particular for the talus. In the literature, the etiopathogenetic mechanism of trauma is favored. Several studies show an anamnestic coincidence of distorsion and/or supination trauma prior to the onset of o.d. at the talus.The most common localization of the o.d. lesion is the middle and posterior third of the medial and less frequently anterior and middle third of the lateral talus. Biomechanical experiments demonstrated that these areas are those with the highest load under varus/valgus and pronation/supination stress.Trauma is held responsible for both the more frequent medial, cup-shaped lesion and the less frequent lateral, wafer-shaped lesion. Taking into consideration the complex motion patterns of the ankle joint, these conceptions should be abandoned and the exact pathomorphogenetic mechanism assessed more closely in future. Other possible etiological factors such as genetic, metabolic or infectious causes are discussed but are not yet substantiated by scientific and experimental evidence.The different stages of o. d. do not differ from the stages in other joints and from aseptic osteonecrosis. Theoretically, it seems that o.d. is initiated when an imaginary threshold value is reached so that a subchondral osteonecrosis occurs (stage I). Repetitive mechanical forces possibly interfere with the regeneration process of the lesions, resulting in the development of a subchondral sclerosis (stage II). Further disturbance of the regenerative process may lead to a demarcation of the osteochondral area (stage III) and eventually dissecation (stage IV) of the fragment with loose bodies in the joint.Clinical symptoms are nonspecific. Periarticular swelling, hydrarthrosis, reduced range of motion and sometimes joint locking are the most common clinical signs. Differentiation of o.d. from posttraumatic osteochondral lesions of the talus is sometimes difficult or even impossible. In contrast, other entities of the tibiotalar joint (such as talar necrosis or subchondral ganglion) can be easily distinguished.

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.

Changes in canine skeletal muscles during experimental tibial lengthening.

In 24 beagles, lengthening of the right tibia was performed by callus distraction after osteotomy and application of a ring fixator. Distraction was started at the fifth postoperative day, with a distraction rate of 0.5 mm twice per day, and ended after 25 days. A control group of six additional dogs underwent tibial osteotomy and external fixation without distraction. Twelve animals with and three animals without leg lengthening were euthanized immediately after the distraction period of 25 days (Group A); the remaining 15 dogs were euthanized after an additional consolidation phase of another 25 days (Group B). From the distracted right leg and from the left control leg the tibialis anterior muscle, extensor digitorum longus muscle, peroneus longus muscle, and gastrocnemius muscle were removed and studied by means of routine histologic, histochemical, and immunohistochemical analyses, and electron microscopic examination. The muscles of the control group showed no differences between the right and left sides. However, in the other 24 dogs of Groups A and B, the authors saw marked alterations affecting only the lengthened muscles but not the muscles of the control limbs. These changes were highly significant and included muscle fiber degeneration and regeneration, target fibers, central cores, minicores, marked endomysial and perimysial fibrosis, and atrophy of Type 1 and Type 2 fibers. In the consolidation period (Group B) fiber type grouping indicated that reinnervation had occurred. In addition, an increase in satellite cells and myoblasts and proliferation of nuclei were observed. The findings of the current study indicate that leg lengthening results not only in muscle fiber degeneration followed by regeneration and reinnervation but also in formation of new muscle tissue.

Dislocation of the polyethylene liner in hip arthroplasty: 6 patients with dislocation within 3 years.

We revised 6 patients with early destruction of the liner in a cementless press-fit acetabular cup. They had no signs of infection or evidence of trauma. The failures were probably due to rotation of the liner inside the metal shell and destruction of the polyethylene by the cutting edge of the metal. This early complication may be difficult to diagnose because of normal radiographs. We suggest that the manufacturer should provide the insert with a metal marker to make this complication easier to detect.

Morphological study of synovial changes in two-stage reconstructions of the infected hip and knee arthroplasties

Objectives To study the morphological changes of the regenerating synovium in two-stage revision arthroplasty, which is the gold standard for treatment of periprosthetic joint infection. Design The authors analysed a series of synovial biopsies to examine morphological changes in healing periprosthetic tissues damaged by previous surgery and infection. Methods Synovial tissues from 19 patients (10 knees and 9 hips) who underwent a two-stage exchange surgery for periprosthetic infection were reviewed and correlated with clinical and laboratory findings. Setting Retrospective morphological study. Participants Archival tissues from 19 two-stage revision arthroplasties in adult patients. Results Healing synovial tissue obtained at the reimplantation surgery showed characteristic layering: superficial fibrin exudate, immature richly vascularised granulation tissue and deeper maturing granulation tissue and fibrosis. Although increased neutrophil counts were found in the majority of cases, 2 of 19 cases showed dense infiltrates indicative of persistent infection, which correlated with positive microbiology in one case. One of the cases failed due to acetabular loosening and two cases failed due to late superinfection. One case showed a dense infiltration of eosinophils suggestive of a hypersensitivity reaction, which was subsequently proven by cutaneous tests. Foci of extramedullary haematopoiesis were detected in two cases. Conclusions We observed characteristic morphological changes in the healing synovial tissue during reimplantation surgery for periprosthetic infection in serologically and microbiologically sterile tissues. Substantial increased counts of synovial neutrophils (>200 cells/10 high-power fields) seem to be indicative of persistent infection of the joint; therefore, prolonged antibiotic therapy should be considered in positive cases.

Long-term results of the thrust plate prosthesis in patients with rheumatoid arthritis: a minimum 10-year follow-up

BackgroundThe thrust plate prosthesis (TPP) is a hip prosthesis with metaphyseal fixation to the femur. Because the bone quality is reduced in patients with rheumatoid arthritis, this kind of fixation may have a higher failure rate than conventional stemmed endoprostheses in these patients. The aim of this investigation was to analyze the long-term results obtained with the TPP in patients with rheumatoid arthritis.MethodsThe survival of 51 implants in 46 patients with rheumatoid arthritis was analyzed. Clinical (Harris hip score) and radiological examinations were carried out on 47 of the 51 TPPs, with a post implantation follow-up period of at least 10 years. The Kaplan-Meier method was used to estimate the survival rates of the TPPs, with surgical revision due to the femoral implant as the endpoint of the investigation.ResultsThe Harris hip score increased from 42.4 ± 6.5 points preoperatively to 86.6 ± 10.1 points at follow-up. The failure rate was 23% (6 aseptic and 5 septic loosening). The total rate of revision amounted to 36.2% (17/47 TPPs): six aseptic loosening of TPPs, five septic loosening of TPPs, four aseptic loosening of the acetabular component, one removal of the fishplate of a TPP, and one femoral fracture. Additionally one TPP showed radiolucent lines indicating prosthetic loosening. Revision surgeries to stemmed endoprostheses of the hip were without severe problems in any patients.ConclusionsThe failure rate of the TPP was distinctly higher than that for conventional stemmed endoprostheses regarding aseptic and septic revisions. In cases with loosening of the TPP the preservation of the diaphyseal bone of the femur is poor and the TPP mostly needs a revision to a cemented stem. Thus, the estimated advantage of the TPP versus cementless stemmed prostheses for patients with rheumatoid arthritis is not evident. In conclusion, there is no evidence form this study to support the use of the TPP in this group of patients.

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.

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.