Andreas Neff

Osteoporosis and bisphosphonates-related osteonecrosis of the jaw: Not just a sporadic coincidence – a multi-centre study

INTRODUCTION Bisphosphonates (BPs) are powerful drugs that inhibit bone metabolism. Adverse side effects are rare but potentially severe such as bisphosphonate-related osteonecrosis of the jaw (BRONJ). To date, research has primarily focused on the development and progression of BRONJ in cancer patients with bone metastasis, who have received high dosages of BPs intravenously. However, a potential dilemma may arise from a far larger cohort, namely the millions of osteoporosis patients on long-term oral BP therapy. PATIENTS AND METHODS This current study assessed 470 cases of BRONJ diagnosed between 2004 and 2008 at eleven different European clinical centres and has resulted in the identification of a considerable cohort of osteoporosis patients suffering from BRONJ. Each patient was clinically examined and a detailed medical history was raised. RESULTS In total, 37/470 cases (7.8%) were associated with oral BP therapy due to osteoporosis. The majority (57%) of affected individuals did not have any risk factors for BRONJ as defined by the American Association of Oral and Maxillofacial Surgery. The average duration of BP intake of patients without risk factors was longer and the respective patients were older compared to patients with risk factors, but no statistical significant difference was found. In 78% of patients the duration of oral BP therapy exceeded 3 years prior to BRONJ diagnosis. DISCUSSION The results from this study suggest that the relative frequency of osteoporosis patients on oral BPs suffering from BRONJ is higher than previously reported. There is an urgent need to substantiate epidemiological characteristics of BRONJ in large cohorts of individuals.

Microcystic Lymphatic Malformations of the Tongue Diagnosis, Classification, and Treatment

OBJECTIVE To describe a classification of microcystic lymphatic malformations of the tongue and to investigate different treatment methods. DESIGN Retrospective review of patients treated for microcystic lymphatic malformations of the tongue. Lymphatic malformations were classified into the following 4 groups according to their extent: isolated superficial microcystic lymphatic malformations of the tongue (stage I); isolated lymphatic malformations of the tongue with muscle involvement (stage II; stage IIA, involving a part of the tongue; stage IIB, involving the entire tongue); microcystic lymphatic malformations of the tongue and the floor of mouth (stage III); and extensive microcystic lymphatic malformations involving the tongue, floor of mouth, and further cervical structures (stage IV). PATIENTS Twenty patients with microcystic lymphatic malformation of the tongue. MAIN OUTCOME MEASURES Medical records were reviewed for demographic data and extent and treatment of the lymphatic malformations. RESULTS Three patients had stage I disease; 5 patients, stage II; 3 patients, stage III; and 9 patients, stage IV. In 6 patients, the lymphatic malformations could be completely removed by carbon dioxide laser surgery; the remaining 13 patients had persistent disease. CONCLUSIONS The initial stage seems to predict outcome. Carbon dioxide laser therapy provides good results primarily in stages I and IIA lymphatic malformations. In advanced lymphatic malformations (stages IIB, III, and IV), an interdisciplinary approach is necessary, because complete surgical excision is often impossible owing to the diffuse growth behavior, and therefore recurrence and persistence are common.

The Comprehensive AOCMF Classification System: Condylar Process Fractures - Level 3 Tutorial

This tutorial outlines the detailed system for fractures of the condylar process at the precision level 3 and is organized in a sequence of sections dealing with the description of the classification system within topographical subdivisions along with rules for fracture coding and a series of case examples with clinical imaging. Basically, the condylar process comprises three fracture levels and is subdivided into the head region, the condylar neck, and the condylar base. Fractures of the condylar head show typical fracture lines either within the lateral pole zone, which may lead to loss of vertical height, or medially to the pole zone, with the latter ones usually not compromising the vertical condyle to fossa relation. In condylar head fractures, the morphology is further described by the presence of minor or major fragmentation, the vertical apposition of fragments at the plane of the head fracture, the displacement of the condylar head with regard to the fossa including a potential distortion of the condylar head congruency resulting in dystopic condyle to fossa relations and the presence or absence of a loss of vertical ramus height. A specific vertical fracture pattern extending from the head to the neck or base subregion is considered. Fractures of the condylar neck and base can be differentiated according to a newly introduced one-third to two-thirds rule with regard to the proportion of the fracture line above and below the level of the sigmoid notch, which is presented in the classification article, and are basically subdivided according to the presence or absence of displacement or dislocation. In both condylar neck and base fractures, the classification is again based on the above mentioned parameters such as fragmentation, displacement of the condylar head with regard to the fossa, including dystopic condyle to fossa relations and loss of vertical ramus height, that is, according to the measurement of the condylar process. In addition, the classification assesses a sideward displacement including the respective displacement sector at the neck or base fracture site as well as the angulation of the superior main fragment and also considers a potential displacement of the caudal fragment with regard to the fossa, which may occur in fractures affecting additional fracture locations in the mandible. The design of this classification is discussed along with a review of existing classification systems. The condylar process for fracture location was defined according to the level 2 system presented in a previous tutorial in this special issue.

New advances in fluorochrome sequential labelling of teeth using seven different fluorochromes and spectral image analysis

Fluorochrome sequential labelling of mineralizing tissues is commonly used in different fields of clinical and basic research. Recently we improved polychrome fluorescent sequential labelling of bone by applying spectral image analysis to discriminate seven different fluorochromes. Although basic mineralization processes of bone and teeth follow comparable principles, the respective tissues differ in terms of matrix composition and mineral assembly. The aim of this study therefore was to investigate the feasibility of this new technique for polychrome sequential labelling of teeth and to demonstrate the advantages in the field of dentistry. Furthermore, the exact labelled area of each fluorochrome could be measured, even in regions of overlapping fluorochromes. The technique presented may provide a basis for further investigations of mineralization processes of different anatomical dental structures.

Position paper from the IBRA Symposium on Surgery of the Head – The 2nd International Symposium for Condylar Fracture Osteosynthesis, Marseille, France 2012

BACKGROUND This is a position paper from the 2nd International Bone Research Association (IBRA) Symposium for Condylar Fracture Osteosynthesis 2012 was held at Marseille, succeeding the first congress in Strasbourg, France, in 2007. The goal of this IBRA symposium and this paper was to evaluate current trends and potential changes of treatment strategies for mandibular condylar fractures, which remain controversial over the past decades. METHODS Using a cross-sectional study design, we enrolled the consensus based on the panel of experts and participants in the IBRA Symposium 2012. The outcomes of interest were the panel and electronic votes on management of condylar base, neck and head fractures, and panel votes on endoscopic and paediatric condylar fractures. Appropriate descriptive and univariate statistics were used. RESULTS The consensus derived from 14 experts and 41 participant surgeons, using 12 case scenarios and 27 statements. The experts and participants had similar decision on the treatment of condylar base, neck and head fractures, as well as similar opinion on complications of condylar fracture osteosynthesis. They had a parallel agreement on using open reduction with internal fixation (ORIF) as treatment of choice for condylar base and neck fractures in adults. Endoscopic approaches should be considered for selected cases, such as condylar base fractures with lateral displacement. There was also a growing tendency to perform ORIF in condylar head fractures. The experts also agreed to treat children (>12 years old) in the same way as adults and to consider open reduction in severely displaced and dislocated fractures even in younger children. Nevertheless, non-surgical treatment should be the first choice for children <6 years of age. The decision to perform surgery in children was based on factors influencing facial growth, appropriate age for ORIF, and disagreement to use resorbable materials in children. CONCLUSIONS The experts and participating surgeons had comparable opinion on management of condylar fractures and complications of ORIF. Compared to the first Condylar Fracture Symposium 2007 in Strasbourg, ORIF may now be considered as the gold standard for both condylar base and neck fractures with displacement and dislocation. Although ORIF in condylar head fractures in adults and condylar fractures in children with mixed dentition is highly recommended, but this recommendation requires further investigations.

The current state of facial prosthetics – A multicenter analysis

Even though modern surgical techniques are dominating reconstructive facial procedures, the capability to use facial epitheses for reconstruction is still an important skill for the maxillofacial surgeon. We present an international multicenter analysis to clarify which techniques are used to fixate facial prostheses. We contacted all maxillofacial departments in Germany, Austria, Switzerland and Norway which were registered with the German society for oral and maxillofacial surgery (DGMKG). These centers were asked via electronical mail to provide information on the type of epithesis fixation systems currently in use. The return rate from 58 departments was 43.1% (n = 25). Overall, implant fixation was the preferred fixation system (92%). Plates were the second most common fixation technique (32%). No centers reported the standard use of non-invasive fixation techniques for permanent epithesis fixation. The main retention systems in use were magnets (24/25), other retention systems are used much less often. The current preferred fixation technique for facial epitheses consists of implant-based, magnet-fixated epitheses. For nasal prostheses, a plate-based, magnet-fixated system is often used.

The Comprehensive AOCMF Classification System: Fracture Case Collection, Diagnostic Imaging Work Up, AOCOIAC Iconography and Coding

The AO classification system for fractures in the adult craniomaxillofacial (CMF) skeleton is organized in anatomic modules in a 3 precision-level hierarchy with account for an increasing complexity and details. Level-1 is most elementary and identifies no more than the presence of fractures in 4 separate anatomical units: the mandible (code 91), midface (92), skull base (93) and cranial vault (94). Level-2 relates the detailed topographic location of the fractures within defined regions of the mandible, central and lateral midface, internal orbit, endo- and exocranial skull base, and the cranial vault. Level-3 is based on an even more refined topographic assessment and focuses on the morphology — fragmentation, displacement, and bone defects — within specified subregions. An electronic fracture case collection complements the preceding tutorial papers, which explain the features and options of the AOCMF classification system in this issue of the Journal. The electronic case collection demonstrates a range of representative osseous CMF injuries on the basis of diagnostic images, narrative descriptions of the fracture diagnosis and their classification using the icons for illustration and coding of a dedicated software AOCOIAC (AO Comprehensive Injury Automatic Classifier). Ninety four case examples are listed in two tables for a fast overview of the electronic content. Each case can serve as a guide to getting started with the new AOCMF classification system using AOCOIAC software and to employ it in the own clinical practice.

Die Maßhaltigkeit von Stereolithographiemodellen für Operationsplanungen

EINLEITUNG Die Chirurgie des Gesichtsschädels erfordert hohe Präzision in der Diagnostik, der Operationsplanung und deren Umsetzung am Patienten. Vor allem bei der Planung von sehr komplexen kraniofazialen KorrektureingrifFen haben 3D-CT Schädelmodelle, hergestellt über Rapid-Prototyping-Verfahren (RP), d.i. die schnelle maßstabsgetreue Produktion dreidimensionaler Körper aus beliebigen SDDatensätzen,, inzwischen einen hohen Stellenwert. In der Mund-Kiefer-Gesichtschirurgie werden vorwiegend Schädelmodelle eingesetzt, die anhand von CT-Datensätzen über das Stereolithographie-Verfahren (STL) erstellt werden. Es wurde wie die anderen RP-Verfahren zunächst für die Industrie entwickelt [1]. Bevorzugt wird dieses Verfahren wegen der Transparenz des verwendeten Materials, das eine sehr gute Beurteilung anatomischer Formen mit innen l legenden Hohlräumen erlaubt, und wegen der guten Bearbeitungsmöglichkeit für eine präoperative Simulation individueller Osteotomien. [2, 3 9]Da die anatomische Genauigkeit bei einem Millimeter liegen muß, ist der Anspruch dieser Modelle auf anatomische Genauigkeit ausschlaggebend für deren klinische Einsetzbarkeit [10]. Allein beim Herstellungsprozeß können eine Vielzahl chemischer und mechanischer Faktoren die Genauigkeit des Ergebnisses beeinflussen [7]. Nach klinischer Erfahrung mit 148 angefertigten Schädelmodellen in den Jahren 1992-1997 stellte sich die Frage, ob dieses Verfahren schon so sicher und standardisiert ist, daß es in der klinischen Routine als etabliert angesehen werden kann. Schließlich ist eine Vielzahl von Arbeitsschritten Datenakquisition, Dateriprocessing und die eigentliche STL-Modellherstellung notwendig, die entsprechende Fehlermöglichkeiten implizieren. Die Erfahrungen mit diesen Modellen wurden daher retrospektiv ausgewertet und auf mögliche Konsequenzen für die klinische Praxis untersucht.

Epidermal growth factor-induced modulation of cytokeratin expression levels influences the morphological phenotype of head and neck squamous cell carcinoma cells

The migratory ability of tumor cells requires cytoskeletal rearrangement processes. Epidermal growth factor receptor (EGFR)-signaling tightly correlates with tumor progression in head and neck squamous cell carcinomas (HNSCCs), and has previously been implicated in the regulation of cytokeratin (CK) expression. In this study, HNSCC cell lines were treated with EGF, and CK expression levels were monitored by Western blot analysis. Changes in cellular morphology were documented by fluorescence- and atomic force microscopy. Some of the cell lines demonstrated an EGF-dependent modulation of CK expression levels. Interestingly, regression of some CK subtypes or initial up-regulation followed by downregulation at higher EGF-levels could also be observed in the tested cell lines. Overall, the influence of EGF on CK expression levels appeared variable and cell-type-dependent. Real-time cellular analysis of EGF-treated and -untreated HNSCC cell lines demonstrated a rise over time in cellular impedance. In three of the EGF-treated HNSCC cell lines, this rise was markedly higher than in untreated controls, whereas in one of the cell lines the gain of cellular impedance was paradoxically reduced after EGF treatment, which was found to correlate with changes in cellular morphology rather than with relevant changes in cellular viability or proliferation. After treating HNSCC cells with EGF, CK filaments frequently appeared diffusely distributed throughout the cytoplasm, and in some cases were found in a perinuclear localization, the latter being reminiscent to observations by other groups. In summary, the data points to a possible role of EGFR in modulating HNSCC cell morphology.

Möglichkeiten und Indikationsbereiche der kohlenstoffaserverstärkten Kunststoffe zur Herstellung individueller Implantate für die Rekonstruktion des Gesichts- und Hirnschädels

EINLEITUNG Rekonstruktionen am Hirnund Gesichtsschädel sind wegen der komplexen Formverhältnisse sehr schwierig. Durch den Einsatz innovativer SD-Technologien (Stereolithographie, Selektives Lasersintern) können jedoch an individuellen anatomischen Modellen Implantate mit kompliziertesten Formgebungen gestaltet werden. In der Mund-Kiefer-Gesichtschirurgie werden diese Technologien genutzt, um individuelle Implantate aus kohlenstoffaserverstärkten Verbundwerkstoffen bei kraniofazialen Rekonstruktionen einzusetzen [6].