Osteonecrose maxilar associada ao uso de bisfosfonatos

Os bisfosfonatos (BFs) têm sido indicados para o tratamento de doenças do metabolismo ósseo. Atualmente, seu emprego terapêutico aumentou e, com ele, os efeitos adversos, dos quais um dos mais importantes é a indução da osteonecrose dos maxilares, uma complicação de difíceis tratamento e solução. Até o presente, não se sabe ao certo qual é o mecanismo de desenvolvimento da osteonecrose dos maxilares induzida por bisfosfonatos (ONMB), nem qual deve ser o tratamento estabelecido perante essa manifestação. Apesar de a literatura apresentar formas variadas de tratamento, não existe um protocolo definido. Apresentamos uma revisão sobre a ONMB, enfocando sua etiopatogenia e as formas reportadas de tratamento.

Osteonecrosis de los maxilares asociada a bisfonatos

Programa de doctorado: Avances en medicina interna.

Jaw mechanics of the pterosaur skull construction and the evolution of toothlessness

In the present study, pterosaur skull constructions were analysed using a combined approach of finite element analysis (FEA), static investigations as well as applying classical beam theory and lever mechanics. The study concentrates on the operating regime „bite“, where loads are distributed via the dentition or a keratinous rhamphotheca into the skull during jaw occlusion. As a first step, pterosaur tooth constructions were analysed. The different morphologies of the tooth construction determine specific operational ranges, in which the teeth perform best (= greatest resistance against failure). The incomplete enamel-covering of the pterosaur tooth constructions thereby leads to a reduction of strain and stress and to a greater lateral elasticity than for a complete enamel cover. This permits the development of high and lateral compressed tooth constructions. Further stress-absorption occurs in the periodontal membrane, although its mechanical properties can not be clarified unambiguously. A three-dimensionally preserved skull of Anhanguera was chosen as a case-study for the investigation of the skull constructions. CT-scans were made to get information about the internal architecture, supplemented by thin-sections of a rostrum of a second Anhanguera specimen. These showed that the rostrum can be approximated as a double-walled triangular tube with a large central vacuity and an average wall-thickness of the bony layers of about 1 mm. On base of the CT-scans, a stereolithography of the skull of Anhanguera was made on which the jaw adductor and abductor muscles were modelled, permitting to determine muscular forces. The values were used for the lever mechanics, cantilever and space frame analysis. These studies and the FEA show, that the jaw reaction forces are critical for the stability of the skull construction. The large jugal area ventral to the orbita and the inclined occipital region act as buttresses against these loads. In contrast to the orbitotemporal region which is subject to varying loading conditions, the pattern in the rostrum is less complex. Here, mainly bending in dorsal direction and torsion occur. The hollow rostrum leads to a reduction of weight of the skull and to a high bending and torsional resistance. Similar to the Anhanguera skull construction, the skulls of those pterosaur taxa were analysed, from which enough skull material is know to permit a reliable reconstruction. Furthermore, FEA were made from five selected taxa. The comparison of the biomechanical behaviour of the different skull constructions results in major transformational processes: elongation of rostra, inclination of the occipital region, variation of tooth morphology, reduction of the dentition and replacement of teeth by a keratinous hook or rhamphotheca, fusion of naris and antorbital fenestra, and the development of bony and soft-tissue crests. These processes are discussed for their biomechanical effects during bite. Certain optional operational ranges for feeding are assigned to the different skull constructions and previous hypotheses (e.g. skimming) are verified. Using the principle of economisation, these processes help to establish irreversible transformations and to define possible evolutionary pathways. The resulting constructional levels and the structural variations within these levels are interpreted in light of a greater feeding efficiency and reduction of bony mass combined with an increased stability against the various loads. The biomechanical conclusive pathways are used for comparison and verification of recent hypothesis of the phylogenetic systematics of pterosaurs.

Bisphosphonat-assoziierte Osteonekrose der Kiefer : In-vitro-Untersuchungen zur Pathologie und zu möglichen Therapieansätzen

Die Bisphosphonat-assoziierte Osteonekrose der Kiefer (BP-ONJ) stellt eine ernstzunehmende Nebenwirkung der Therapie mit stickstoffhaltigen Bisphosphonaten (N-BP) dar, deren Ätiologie bisher noch nicht vollständig geklärt ist. Da entzündliche Prozesse eine wichtige Rolle zu spielen scheinen, wurde der Einfluss verschiedener Bisphosphonate auf die Mechanismen der granulozytären Erregerabwehr untersucht. Die N-BP Ibandronat, Pamidronat und Zoledronat steigerten die Phagozytose und den oxidativen Burst signifikant. Die fMLP-stimulierte Chemotaxis wurde durch Ibandronat und Zoledronat signifikant reduziert. Das stickstofffreie Clodronat zeigte keinen Effekt auf die getesteten Abwehrmechanismen. Auf der Suche nach therapeutischen Optionen gegen die BP-ONJ wurden die Isoprenoide Farnesol, Geranylgeraniol, Eugenol, Menthol, Limonene und Squalene auf deren Fähigkeit untersucht, die schädigenden Effekte Zoledronats auf verschiedene Zelllinien zu antagonisieren. Geranylgeraniol zeigte als einzige Verbindung eine protektive Wirkung auf gingivale Fibroblasten, Endothelzellen und Osteoblasten. Desweiteren kam es unter Zoledronat zum Anstieg der kleinen GTPasen RhoA und RhoB in gingivalen Fibroblasten. Auch der Gehalt an GTP-gebundenem RhoA stieg nach Zoledronat-Inkubation. Der Einfluss des N-BPs ließ sich auch auf Proteinebene durch Geranylgeraniol antagonisieren und nicht durch Farnesol. Die Tatsache, dass N-BP die granulozytäre Abwehr beeinflussen, unterstützt die Bedeutung keimreduzierender Maßnahmen im Rahmen der Nekroseprophylaxe und -therapie. Außerdem untermauern die Ergebnisse der Arbeit das Potential Geranylgeraniols als neue therapeutische Option.

Analysis of 3D Soft Tissue Changes After 1- and 2-Jaw Orthognathic Surgery in Mandibular Prognathism Patients

Purpose Orthognathic surgery has the objective of altering facial balance to achieve esthetic results in patients who have severe disharmony of the jaws. The purpose was to quantify the soft tissue changes after orthognathic surgery, as well as to assess the differences in 3D soft tissue changes in the middle and lower third of the face between the 1- and 2-jaw surgery groups, in mandibular prognathism patients. Materials and Methods We assessed soft tissue changes of patients who have been diagnosed with mandibular prognathism and received either isolated mandibular surgery or bimaxillary surgery. The quantitative surface displacement was assessed by superimposing preoperative and postoperative volumetric images. An observer measured a surface-distance value that is shown as a contour line. Differences between the groups were determined by the Mann-Whitney U test. The Spearman correlation coefficient was used to evaluate a potential correlation between patients' surgical and cephalometric variables and soft tissue changes after orthognathic surgery in each group. Results There were significant differences in the middle third of the face between the 1- and 2-jaw surgery groups. Soft tissues in the lower third of the face changed in both surgery groups, but not significantly. The correlation patterns were more evident in the lower third of the face. Conclusion The overall soft tissue changes of the midfacial area were more evident in the 2-jaw surgery group. In 2-jaw surgery, significant changes would be expected in the midfacial area, but caution should be exercised in patients who have a wide alar base.

[Implant-supported bridges in the edentulous jaw. Clinical aspects of a simple treatment concept]

Clinical aspects of a simple treatment concept with fixed prostheses in the edentulous jaw are described. Fixed implant-supported reconstructions in the edentulous jaw require multiple implants, are technically complex, aesthetically demanding and metal-ceramic solutions are expensive. Specific surgical techniques to enhance the hard and soft tissue conditions become often necessary. Thus the bar-supported overdenture may be preferred, because problems with aesthetics and alveolar ridge deficiencies can be solved more easily and the number of implants is reduced. Both, the "All-on-Four" technique and the "Procera implant bridge" are simple type of fixed prostheses, comparable to overdentures or complete dentures with regard to design and technology. They present a cost-effective alternative, with predictable aesthetics and optimum passive fit.

A new system for computer-aided preoperative planning and intraoperative navigation during corrective jaw surgery

A new system for computer-aided corrective surgery of the jaws has been developed and introduced clinically. It combines three-dimensional (3-D) surgical planning with conventional dental occlusion planning. The developed software allows simulating the surgical correction on virtual 3-D models of the facial skeleton generated from computed tomography (CT) scans. Surgery planning and simulation include dynamic cephalometry, semi-automatic mirroring, interactive cutting of bone and segment repositioning. By coupling the software with a tracking system and with the help of a special registration procedure, we are able to acquire dental occlusion plans from plaster model mounts. Upon completion of the surgical plan, the setup is used to manufacture positioning splints for intraoperative guidance. The system provides further intraoperative assistance with the help of a display showing jaw positions and 3-D positioning guides updated in real time during the surgical procedure. The proposed approach offers the advantages of 3-D visualization and tracking technology without sacrificing long-proven cast-based techniques for dental occlusion evaluation. The system has been applied on one patient. Throughout this procedure, we have experienced improved assessment of pathology, increased precision, and augmented control.

Minimum ten year results of total hip arthroplasty with the acetabular reinforcement ring in avascular osteonecrosis

Total hip arthroplasty (THA) still carries a higher failure rate in patients with avascular necrosis of the femoral head (AVN) than in a similar patient population with THA for other reasons. This is particularly true for the acetabular component. One of the major factors accounting for this is the compromised acetabular bone quality with structural defects subsequent to collapsing of the femoral head in high-grade AVN. In this study we implanted an acetabular reinforcement ring with hook (ARRH), which had been used successfully for other indications with acetabular bone stock deficiency, in 32 consecutive THA's in 29 patients with AVN. Five patients died during the observation period of causes unrelated to the surgery, one patient was lost to follow-up and one patient could not be followed up due to chronic illness, leaving 25 hips (23 patients) with a minimum follow-up of ten years (mean: 11.8; range: 10-15). The mean Merle d'Aubigne score increased significantly from 7.7 preoperatively to 16.6 postoperatively (p < 0.001). One revision was performed for aseptic stem loosening. Of the unrevised hips, one acetabular component was classified as definitively loose. The cumulative 12-year survivorship for THA with ARRH in AVN was 95.2% (confidence interval: 86.1-100%) for both components, 100% for the cup and 95.2% for the stem (86.1-100%).

CECOG experts' recommendations on the use of denosumab in the prevention of skeletal-related events in bone metastases of lung cancer

Purpose Skeletal-related events represent a substantial burden for patients with advanced cancer. Randomized, controlled studies suggested superiority of denosumab over zoledronic acid in the prevention of skeletal-related events in metastatic cancer patients, with a favorable safety profile. Experts gathered at the 2012 Skeletal Care Academy in Istanbul to bring forward practical recommendations, based on current evidence, for the use of denosumab in patients with bone metastases of lung cancer. Recommendations Based on current evidence, use of denosumab in lung cancer patients with confirmed bone metastases is recommended. It is important to note that clinical judgment should take into consideration the patient’s general performance status, overall prognosis, and live expectancy. Currently, the adverse event profile reported for denosumab includes hypocalcemia and infrequent occurrence of osteonecrosis of the jaw. Therefore, routine calcium and vitamin D supplementation, along with dental examination prior to denosumab initiation are recommended. There is no evidence for renal function impairment due to denosumab administration. At present, there is no rationale to discourage concomitant use of denosumab and surgery or radiotherapy.