H. Plenk

Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1

Bone formation by osteoblasts is essential for skeletal growth and remodeling. Fra-1 is a c-Fos-related protein belonging to the AP-1 family of transcription factors. Here we show that transgenic mice overexpressing Fra-1 in various organs develop a progressive increase in bone mass leading to osteosclerosis of the entire skeleton, which is due to a cell-autonomous increase in the number of mature osteoblasts. Moreover, osteoblast differentiation, but not proliferation, was enhanced and osteoclastogenesis was also elevated in vitro. These data indicate that, unlike c-Fos, which causes osteosarcomas, Fra-1 specifically enhances bone formation, which may be exploited to stimulate bone formation in pathological conditions.

Long-term results of uncemented alumina acetabular implants

We report the clinical and tribological performance of 67 ceramic acetabular prostheses implanted between 1976 and 1979 without bone cement. They articulated with ceramic femoral heads mounted on mental femoral stems. After a mean elapsed period of 144 months, 59 sockets were radiographically stable but two showed early signs and six showed late signs of loosening. Four of the loose sockets have been revised. Histological analysis of the retrieved tissue showed a fibrous membrane around all the implants, with fibrocartilage in some. There was no bone ingrowth, and the fibrous membrane was up to 6 mm thick and infiltrated with lymphocytes, plasma cells, and macrophages. Intra- and extracellular birefringent wear particles were seen. Tribological analysis showed total wear rates in two retrieved alumina-on-alumina joints of 2.6 microns per year in a stable implant and 68 microns in a loose implant. Survival analysis showed a revision rate of 12.4% at 136 months.

Cochlear Implant Deep Electrode Insertion: Extent of Insertional Trauma

We have recently undertaken deep insertions of the Combi-40 cochlear implant electrode (Med-E1 Corp., Innsbruck, Austria) into apical regions of the scala tympani using a cochleostomy approach. In order to examine the extent of the insertional trauma, 12 fresh human temporal bones were implanted with original Combi-40 electrodes. The specimens were histologically processed with the implants in place by employing a sawing and grinding technique. In most cases, only very discrete distortions of the epithelium of the spiral ligament occurred within the middle cochlear turns. Furthermore, a slight displacement of the basilar membrane caused by the electrode was occasionally seen. However, in 2 cases more severe damage such as basilar membrane rupture and electrode displacement was found. Attempts to insert the electrode beyond the point of first resistance resulted in electrode kinking within the basal cochlear turn with subsequent fracture of the osseous spiral lamina. According to our results, deep electrode insertions do not aggravate the insertional trauma provided no force is applied when resistance is felt.

Perimodiolar Electrodes in Cochlear Implant Surgery

Perimodiolar-positioned cochlear implant electrodes have been developed in order to bring the electrode contacts as close as possible to the spiral ganglion cells, which are the target of electrostimulation. This results in lower electrical thresholds, higher dynamic ranges and less channel interaction when compared with normal implant electrodes which are usually located peripherally within the scala tympani. In this study we evaluated 4 different types of perimodiolar electrode: the Clarion Preformed electrode, the Clarion Preformed electrode with positioner, the Nucleus Contour electrode and the Med-El Perimodiolar Combi 40 electrode. These devices require different approaches to achieve a perimodiolar electrode position. The electrodes were inserted in fresh human temporal bones. After processing these bones with the electrodes in situ by employing a sawing, grinding and polishing technique, the inner ear structures as well as the electrode positions could be evaluated in detail. All electrode types studied had a more or less perimodiolar position; however, each type produced a certain amount of trauma to cochlear structures which is discussed in relation to mechanical properties. Further human temporal bone studies with improved perimodiolar cochlear implant electrodes are necessary in order to find an optimized type of electrode.Perimodiolar-positioned cochlear implant electrodes have been developed in order to bring the electrode contacts as close as possible to the spiral ganglion cells, which are the target of electrostimulation. This results in lower electrical thresholds, higher dynamic ranges and less channel interaction when compared with normal implant electrodes which are usually located peripherally within the scala tympani. In this study we evaluated 4 different types of perimodiolar electrode: the Clarion Preformed electrode, the Clarion Preformed electrode with positioner, the Nucleus Contour electrode and the Med-El Perimodiolar Combi 40 electrode. These devices require different approaches to achieve a perimodiolar electrode position. The electrodes were inserted in fresh human temporal bones. After processing these bones with the electrodes in situ by employing a sawing, grinding and polishing technique, the inner ear structures as well as the electrode positions could be evaluated in detail. All electrode types studied had a more or less perimodiolar position; however, each type produced a certain amount of trauma to cochlear structures which is discussed in relation to mechanical properties. Further human temporal bone studies with improved perimodiolar cochlear implant electrodes are necessary in order to find an optimized type of electrode.

Magnetic resonance imaging and histology of repair in femoral head osteonecrosis

Different repair processes affect the clinical course of nontraumatic avascular femoral head osteonecrosis, not just necrotic lesion size and location. Fourteen femoral heads were retrieved at total hip arthroplasty after core decompression treatment, or after conservative treatment was done on 13 male patients diagnosed with different stages of femoral head osteonecrosis. To determine repair types, features of coronal magnetic resonance images were correlated with light microscopy findings on corresponding coronal undecalcified sections and microradiographs of the retrieved femoral heads.In five femoral heads, repair of necrotic bone and marrow remained restricted to the reactive interface for as many as 63 months, producing the diagnostic osteosclerotic rim with adjacent hypervascularity (limited repair). Nine femoral heads showed extension of the repair process into the necrosis. In five femoral heads, predominant resorption of necrotic bone led to femoral head breakdown within 2 to 50 months (destructive repair). In four femoral heads, reparative bone formation had started from subchondral fractures and/or the reactive interface, definitely reducing the size of the necrotic area (reconstructive repair). In the latter, the disease progressed slowly or stopped for as many as 45 months, irrespective of treatments, but elimination of risk factors seemed beneficial. Although core decompression did not always reach the necrotic area and improve repair, it reduced accompanying bone marrow edema and could delay the disease progress. Osteonecrosis with limited repair can be identified on magnetic resonance images obtained at followup, but the similar signal changes of destructive and reconstructive repair cannot be distinguished on magnetic resonance images alone. The evidence of reconstructive repair in nontraumatic osteonecrosis, however, gives hope for treatments that can improve repair to a sufficient creeping substitution of the affected femoral head.

Die „transiente Osteoporose“ als reversible Sonderform der Hüftkopfnekrose

ZusammenfassungEs wird bis heute kontrovers diskutiert, ob die „transiente Osteoporose“ des Hüftgelenks ein eigenständiges, selbstlimitierendes Krankheitsbild, oder eine reversible Sonderform der Osteonekrose (ON) darstellt. Die „transiente Osteoporose“ ist auch unter den Synonymen „Algodystrophie der Hüfte“, „transient marrow edema“ oder „Knochenmarködemsyndrom (KMÖS)“ bekannt. Das klinische Erscheinungsbild besteht aus mechanischen Hüftgelenkschmerzen, ON-Risikofaktoren und einem diffusen Knochenmarködem in der MRT. Die histomorphologischen Veränderungen entsprechen den Frühformen einer ON. Während jedoch das KMÖS einen suffizienten diffusen Reparaturmechanismus zeigt, erfolgt bei der ON nur eine insuffiziente fokale Reparatur in der Randzone der Nekrose. Der klinische Verlauf ist daher völlig unterschiedlich. Während das KMÖS in fast allen Fällen einen reversiblen Spontanverlauf zeigt, kommt es umgekehrt bei der ON ab dem Stadium II zu einer progredienten Zerstörung des Hüftkopfes. Das bevorzugte Behandlungskonzept ist daher die konservative Therapie mit Entlastung für das KMÖS und die operative Therapie für die ON. In einer prospektiven Studie von 43 Hüftgelenken bei Patienten mit KMÖS wurde der klinische, röntgenologische und MRT Verlauf nach Hüftkopfentlastungsbohrung untersucht. Alle Patienten zeigten eine spontane Schmerzerleichterung unmittelbar nach der Entlastungsbohrung und die durchschnittliche Beschwerdedauer von 6 (3–24) Monaten bei konservativer Therapie konnte mit der Entlastungsbohrung auf durchschnittlich 2 Monate reduziert werden. Perioperativ traten keine Komplikationen auf. Basierend auf unseren Erfahrungen mit inzwischen über 100 Patienten mit KMÖS sind wir überzeugt, dass es sich hierbei nicht um ein selbständiges Krankheitsbild sondern vielmehr um eine reversible Sonderform einer ON handelt. Aufgrund der ausgezeichneten klinischen Ergebnisse mit der Hüftkopfentlastungsbohrung empfehlen wir diese operative Behandlungsmethode beim schmerzhaften KMÖS des Hüftgelenks.SummaryThere is still controversy whether transient osteoporosis of the hip joint represents a distinct self-limiting disease, or reflects only an early, reversible subtype of non-traumatic osteonecrosis (ON). Transient osteoporosis has several synonyms: algodystrophy of the hip; transient marrow oedema; or bone marrow oedema syndrome – BMOES. Clinical presentation of BMOES shows mechanical hip joint pain, ON risk factors, and a diffuse bone marrow oedema in MR imaging. Histomorphological changes resemble early ON, but with diffuse sufficient repair in BMOES and focal and insufficient repair only at the border of the necrotic lesion in ON. Therefore the clinical course and outcome are significant different, with restitution occurring in BMOES, while progressive destruction of the joint takes place in ON. So far, the preferred treatment strategies are protected weight bearing for BMOES, but operative treatment for ON. In a prospective study of patients with BMOES, the clinical, radiographic, and MRI course of 43 hip joints after core decompression treatment were investigated. All patients showed immediate relief of pain after surgery and the average duration of symptoms with conservative treatment could be dramatically reduced by core decompression from 6 months down to 2 months. There were no perioperative complications. Based on our experience with over 100 BMOES patients , we are convinced that this syndrome represents not a distinct disease but an early reversible subtype of non-traumatic ON. Due to the excellent clinical results of core decompression, we recommend this operative therapeutical concept in patients with painful BMOES.

Imaging of avascular necrosis of bone

Abstract The etiology of avascular necrosis (AVN) is multifactorial. Independent of its etiology and localization it shows typical pathologies and radiological images. In the early stages localized subchondral edema is characteristic. In 50 % of all cases accompanying joint effusion may be found. Due to necrosis of the cells of bone marrow and bone fibrovascular, reactions with hyperemia can be delineated. These reactions allow us to visualize necrosis indirectly. The best imaging methods are MRI and, to a lesser extent, bone scintigraphy. In later stages calcification as well as new bone formation and microfractures are typically demonstrated and visualized best with plain X-rays and CT. Why reparations in many cases, particularly in the hip, are incomplete and may stop in any stage is unknown. Over years clinically complete silent AVNs are not an uncommon finding. Prognosis depends on the localization and size of the AVN. The number of repair mechanisms is best outlined with contrast-enhanced MRI and return of fatty marrow.

Alumina ceramic bearings for hip endoprostheses: the Austrian experiences.

The current authors review clinical and retrieval experiences with hemispheric monolithic alumina ceramic sockets (Group 1), implanted between 1976 and 1979, and similar modular titanium sockets with alumina ceramic inlays (Group 2), implanted between 1990 and 1995. Both cementless sockets articulated with alumina ceramic femoral ball heads for total hip joint replacements. Clinical followup of patients with hemispheric monolithic alumina ceramic sockets (Group 1, 138 sockets) resulted in a total failure rate of 19.6% after 5 to 20 years. Radiologic analysis of eight stable sockets showed migration of 0.2 mm to 2.89 mm, but in four sockets at risk for late aseptic failure after an average followup of 12.5 years as much as 13.4 mm of migration was seen. Histologic evaluation revealed pseudosynovial membranes as thick as 1 mm with fine birefringent wear particles within mononuclear macrophages around two stable retrieved sockets. The membranes around four loose sockets were 6 to 10 mm thick and also heavily loaded with larger alumina wear particles. After 7 years followup clinical analysis of patients with modular titanium sockets with alumina ceramic inlays (Group 2, 30 sockets) resulted in four revisions, compared with one revision of 50 identical sockets (control group) with polyethylene instead of alumina ceramic inlays. Wear particle analyses in scanning electron microscopy showed significantly more particles (x 10(9) +/- standard deviation/g dry tissue) from the control group (4.26+/-6.38), compared with alumina ceramic bearings of Group 1 (0.70+/-0.79), and of Group 2 (1.62+/-2.13). The alumina particle sizes ranged between 0.13 and 78.38 microm. The mean annual linear wear of 38.8 microm was calculated for the bearings in Group 1, and of 26.94 microm for bearings in Group 2. These results support the good tribologic and biologic performance of alumina ceramic bearings for total hip arthroplasty.

Survival analysis of an uncemented ceramic acetabular component in total hip replacement

SummaryFollow-up examinations of 67 implants of cement-free ceramic sockets show the need for an exact definition of failure, to warrant comparable evaluations of results. Statistical survival analysis offers the possibility of presenting both the incidence of failures and the dates of their occurrence. If only revision surgery with removal of the socket is considered to be a failure, our material shows the “survival quota” of the ceramic socket after 8 years to be 96.7% ± 2.2%. If radiological signs of loosening are included in the evaluation of failures, the “survival quota” of the stable implants is reduced to 81.9% ±6.9%.ZusammenfassungAnhand der Nachuntersuchung von 67 zementfrei implantierten keramischen Füßchenpfannen wird die Notwendigkeit der genauen Definition des Fehlschlages aufgezeigt, um dadurch eine vergleichbare Beurteilung der Ergebnisse zu gewährleisten. Die statistische Methode der Überlebenszeitanalyse bietet die Möglichkeit, sowohl die Häufigkeit der Fehlschläge als such den Zeitpunkt ihres Auftretens darzustellen. Wird ausschließlich die Reoperation mit Austausch der Pfanne als Fehlschlag bewertet, so ergibt sich im eigenen Material nach 8 Jahren eine „Überlebensquote” der keramischen Pfanne von 96,7% ± 2,2. Werden zusätzlich radiologische Lockerungszeichen in die Fehlschlagbeurteilung aufgenommen, so reduziert sich die „Überlebensquote” der stabilen Implantate auf 81,9% ± 6,9.

Pathomorphologische Aspekte und Reparaturmechanismen der Femurkopfosteonekrose

ZusammenfassungNichttraumatische Osteonekrosen (ON) des Femurkopfes zeigen trotz unterschiedlichen pathogenetischen Faktoren meist sehr ähnliche pathomorphologische Veränderungen. Ausdehnung und Lage des nach ischämischen Ereignissen nekrotisch gewordenen subchondralen Knochen- und Knochenmarksegments einerseits, und Art der ausgelösten Reparaturvorgänge anderseits bestimmen den zeitlichen Ablauf und damit das Schicksal dieser Erkrankung des Hüftgelenks.Anhand von 4 ausgewählten Fällen konservativ oder durch Entlastungsbohrung behandelter Femurkopf-ON werden beispielhaft unterschiedlich suffiziente Reparaturmechanismen aufgezeigt und im Hinblick auf derzeitige Therapiekonzepte diskutiert. Diagnostische Kriterien der Magnetresonanztomographiebilder werden mit lichtmikroskopischen Befunden von unentkalkten Dünnschliffen und Mikrotomschnitten der bei Totalgelenkersatz gewonnenen Hüftköpfe verglichen.Im Initialstadium (ARCO 0) und reversiblen Frühstadium der ON (ARCO I) kann es nach inkompletter Ischämie noch zur suffizienten Reparatur kommen. Nach einem ausgeprägten ischämischen Schaden entwickelt sich jedoch das irreversible Frühstadium der ON (ARCO-Stadium 2). In seltenen Ausnahmefällen (kleine Nekroseareale mit medialer Lokalisation) kann es auch jetzt noch zu einer spontanen suffizienten Reparatur kommen. Üblicherweise findet sich aber in diesem ARCO-Stadium 2 mit noch intakter Gelenkfläche kein Umbau des subchondralen nekrotischen Knochen- und Fettmarkgewebes, sondern nur insuffiziente Reparatur durch fibrovaskuläre Invasion und Knochenresorption an der Grenze zum vitalen Knochengewebe. Wiederholter Knochenanbau auf teilresorbierten nekrotischen Trabekeln führt zur sklerotischen Verdichtung dieser pathognomonischen reaktiven Randzone. Unterhalb des Nekroseareals und der reaktiven Randzone kann jedoch der Knochenanbau ebenfalls verstärkt sein, wenn die ON von einem begleitenden Knochenmarksödem umgeben ist. Entlastungsbohrungen im ARCO-Stadium 2, auch wenn sie das Nekroseareal erreicht hatten, können bestenfalls ein Fortschreiten der Erkrankung verzögern, aber nicht zu einer suffizienten Reparatur im Nekroseareal führen. Vielmehr kommt es bei konservativ oder operativ behandelter ON durch überwiegend destruktiven Knochenumbau früher oder später zum Zusammenbruch der Gelenkfläche und damit zum mechanisch instabilen Übergangsstadium der ON (ARCO-Stadium 3). Die subchondrale Fraktur kann jedoch auch von rekonstruktiven Reparaturvorgängen begleitet sein, die mit chondraler und desmaler Knochenneubildung unter dem Frakturspalt durch „schleichenden Gewebeersatz“ das Nekroseareal zwar teilweise verkleinern, aber den Übergang in das Spätstadium der ON mit sekundären Gelenkdestruktionen (ARCO-Stadium 4) nicht verhindern können.Prinzipiell können daher neben suffizienter Reparatur in seltenen Initial-und Frühstadien drei Formen der insuffizienten Reparatur im Nekroseareal unterschieden werden: fehlender Umbau, destruktiver Umbau, oder rekonstruktiver Umbau. Bis heute konnte mit keiner therapeutischen Maßnahme eine völlige Ausheilung der irreversiblen Früh- bis Spätstadien der ON durch rekonstruktiven Umbau erzielt werden. Verbessertes Verständnis von Pathomorphologie und Reparaturmechanismen könnte jedoch zukünftig Therapiekonzepte für eine vollständige Regeneration des Osteonekroseareals ermöglichen.SummaryThe pathomorphologies of non-traumatic femoral head osteonecroses (ON) are usually similar, despite various known pathogenetic factors. The size and position of the subchondral bone and marrow segment, becoming necrotic after the ischemic event(s), and the kind of repair processes determine the time course and thus the fate of this hip joint disease.Four cases of conservatively or core decompression-treated femoral head ON were selected to demonstrate differently effective repair mechanisms which are discussed in respect to existing therapeutic concepts. Diagnostic criteria from magnetic resonance imaging follow-ups were correlated with light microscopy findings on undecalcified ground and microtome sections from femoral heads retrieved at total joint replacement.Initial stage (ARCO 0) and reversible early stage ON (ARCO 1) after incomplete ischemias can apparently show spontaneous sufficient repair. After extensive and complete ischemia, however, ON progresses without detectable changes on plain radiographs into irreversible early stage ON (ARCO stage 2). Only in exceptional cases (with small, medially located necroses), a spontaneous sufficient repair seems possible. Usually, early ARCO stage 2 ON with intact articular surface shows no remodeling of the subchondral necrotic bone and fatty marrow, but only ineffective repair with fibrovascular tissue invasion and bone resorption at the vital bone border. Repeated bone appositions on partly resorbed necrotic trabeculae form the sclerotic rim in this pathognomonic reactive interface. New bone formation can also be increased underneath the necrotic area and reactive interface when surrounded by accompanying bone marrow edema. Core decompression in ARCO stage 2 ON, even if it reaches the necrotic lesion, can at best delay progression of the disease, but never leads to complete reconstruction of the necrotic area. More likely, after both conservative and operative treatment, destructive resorption without effective consecutive bone formation will lead sooner or later to collapse of the articular surface and thus to mechanical instability of transition stage ON (ARCO stage 3). On the other hand, this subchondral fracture can apparently also cause reconstructive repair which, by involving chondral and membranous ossification in this „creeping substitution“, can reduce the necrotic area. However, it cannot prevent progression into late stage ON (ARCO stage 4) with secondary joint destructions.Principally, besides the rare sufficient repair in initial and certain early ON, three forms of insufficient repair in the necrotic area can be distinguished: lack of remodeling, destructive remodeling, and reconstructive remodeling. To date, no therapeutical intervention exists which leads to complete healing of irreversible ON stages by reconstructive repair. Improved understanding of pathomorphology and repair mechanisms, however, could be the basis for future therapeutical concepts which should aim at the complete regeneration of the osteonecrotic area.