Fixed Full Arches Supported by Tapered Implants with Knife-Edge Thread Design and Nanostructured, Calcium-Incorporated Surface: A Short-Term Prospective Clinical Study.

Purpose. To evaluate implant survival, peri-implant bone loss, and complications affecting fixed full-arch (FFA) restorations supported by implants with a knife-edge thread design and nanostructured, calcium-incorporated surface. Methods. Between January 2013 and December 2015, all patients referred for implant-supported FFA restorations were considered for enrollment in this study. All patients received implants with a knife-edge thread design and nanostructured calcium-incorporated surface (Anyridge®, Megagen, South Korea) were restored with FFA restorations and enrolled in a recall program. The final outcomes were implant survival, peri-implant bone loss, biologic/prosthetic complications, and "complication-free" survival of restorations. Results. Twenty-four patients were selected. Overall, 215 implants were inserted (130 maxilla, 85 mandible), 144 in extraction sockets and 71 in healed ridges. Thirty-six FFAs were delivered (21 maxilla, 15 mandible): 27 were immediately loaded and 9 were conventionally loaded. The follow-up ranged from 1 to 3 years. Two fixtures failed, yielding an implant survival rate of 95.9% (patient-based). A few complications were registered, for a "complication-free" survival of restorations of 88.9%. Conclusions. FFA restorations supported by implants with a knife-edge thread design and nanostructured, calcium-incorporated surface are successful in the short term, with high survival and low complication rates; long-term studies are needed to confirm these outcomes.

Dental panoramic indices and fractal dimension measurements in osteogenesis imperfecta children under pamidronate treatment.

OBJECTIVES: To verify radiomorphometric indices and fractal dimension (FD) in dental panoramic radiographs (DPRs) of children with different types of osteogenesis imperfecta (OI) and also to verify the effect of pamidronate (PAM) treatment in such panoramic analyses. METHODS: In this retrospective study, 197 DPRs of 62 children with OI Types I, III and IV who were in treatment with a comparable dosage of intravenous PAM were selected. The mandibular cortical width (MCW), mandibular cortical index, visual estimation of the cortical width and FD of three standardized trabecular and cortical mandibular regions of interest were obtained from the radiographs. Factorial analysis of variance and Fisher test were used to compare FD and MCW measurements in children with different types of OI for different PAM cycles. RESULTS: Children with all types of OI have thinner and more porous mandibular cortices at the beginning of treatment. There were significant differences between MCW and FD of the cortical bone, regarding different types of OI and number of PAM cycles (p = 0.037 and p = 0.044, respectively). FD measurements of the trabecular bone were not statistically different among OI types nor were PAM cycles (p > 0.05). CONCLUSIONS: Children with OI presented cortical bone alterations after PAM treatment. Both MCW and the FD of the cortical bone were higher in children with OI after PAM treatment. It is argued that cortical bone should be considered for analyzing patients with OI, as well as to monitor the progress of PAM treatment.

Bisphosphonate-related osteonecrosis of the jaws - characteristics, risk factors, clinical features, localization and impact on oncological treatment.

INTRODUCTION: Osteonecrosis of the jaw (ONJ) is a serious side-effect of intravenous nitrogen-containing bisphosphonate therapy frequently used in the treatment of malignant diseases. Despite numerous case series published so far studies with detailed investigations into risk factors, the precise localization of ONJ and impact of ONJ on the oncological treatment remain sparse. PATIENTS AND METHODS: This single-centre study collated medical records (2003-2009) of all patients that suffered from ONJ within the Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-University of Munich, Germany. In total, 126 patients fulfilled the case criteria of ONJ and were examined clinically. The complete medical history including detailed questionnaires was collected of 66 patients, focussing in particular on the identification of underlying risk factors, clinical features, ONJ localization as well as the impact on the oncological treatment. RESULTS: The majority of ONJ cases occurred in patients suffering from malignant diseases (n=117; 92.8%), in particular breast cancer (n=57; 45.2%), multiple myeloma (n=37; 29.4%) and prostate cancer (n=13; 10.3%), all received nitrogen-containing bisphosphonates intravenously. ONJ was also diagnosed in 9 patients (7.1%) suffering from osteoporosis or rheumatoid arthritis. The most prevalent clinical feature was exposed necrotic bone (93.9%) in the oral cavity which was accompanied in 78.8% of cases by pain. A predilection for the mandible and in particular for molar and premolar regions in both jaws was shown. Although no recommendation concerning the oncologic treatment was made, the manifestation of ONJ resulted (in a significant proportion of the patients) in a change of medication and schedule. The most frequent co-medications were steroids and anti-angiogenetic drugs, such as thalidomide. DISCUSSION: The predilection for mandibular molar and premolar regions, and the infectious conditions that often precede the onset of ONJ support recent pathogenesis theories stating that local inflammation and associated pH-changes may trigger the release and activation of nitrogen-containing bisphosphonates ultimately resulting in necrosis. CONCLUSION: The development of ONJ has a multi-factorial aetiology and the clinical presentation can vary markedly. ONJ cannot only impair the quality of life but also the treatment of the underlying disease.

Buccal versus lingual articaine infiltration for mandibular tooth anaesthesia: a randomized controlled trial.

AIM: To compare the effectiveness of buccal and lingual local anaesthetic injections in the mandibular first molar region in obtaining pulpal anaesthesia in mandibular teeth. METHODOLOGY: Twenty healthy volunteers received 1.8 mL of 4% articaine with 1 : 100,000 epinephrine as a buccal or lingual infiltration in the mandibular first molar region in a randomized double-blind cross-over design. The responses of the first molar, a premolar and the lateral incisor teeth were assessed using an electronic pulp tester over a 47-min period. Successful anaesthesia was defined as no response to maximum stimulus from the pulp tester on two or more consecutive tests. Success between techniques was analysed using the McNemar test and variations between teeth were compared with Chi-square. RESULTS: The number of no responses to maximum stimulation from an electronic pulp tester was significantly greater for all test teeth after the buccal injection compared with the lingual approach (P < 0.001). Successful anaesthesia was more likely following the buccal infiltration compared with the lingual method for molar (65% and 10%, respectively) and premolar (90% and 15%, respectively) teeth. There was no difference in anaesthetic success for the lateral incisor. CONCLUSION: Buccal infiltration at the first mandibular molar is more effective than lingual infiltration in the same region in obtaining anaesthesia of the mandibular first molar and premolar teeth.

Evaluation of vascular endothelial growth factor (VEGF) in interradicular bone marrow in olpadronate treated animals

Vascular endothelial growth factor (VEGF) is a protein that increases vascular permeability and induces the proliferation, migration and survival of endothelial cells. Bisphosphonates (BPs) are antiresorptive drugs that are widely used in the treatment of bone metabolism diseases and bone metastases. Since 2003, cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) have been reported. Few papers explain the mechanisms that induce BRONJ; some authors mention alterations in bone remodelling and a certain antiangiogenic effect of BPs. The aim of this study is to evaluate the expression of VEGF in bone marrow cells and the number of blood vessels and area occupied by them in animals treated with the BP sodium olpadronate (OPD). We used 16 Wistar rats, 60 days old, divided into two groups, experimental (OPD) and control. The OPD group received 0.3 mg/kg/week intraperitoneal OPD for 5 weeks. The control group received an equivalent intraperitoneal volume of physiological saline solution. After euthanasia, hemimandibles were processed and mesio-distal histological sections of the first molar were prepared. Sections were stained with hematoxylin-eosin (HE), immunohistochemical detection of VEGF was performed (sc- 7269) and the following histomorphometric parameters were evaluated: In HE-stained sections - number of blood vessels per sq. mm. and percentage (%) of area occupied by blood vessels in relation to total area evaluated; in sections with immunohistochemical detection of VEGF – number of VEGF+ bone marrow cells per sq. mm. Data underwent statistical analysis. Number of blood vessels/mm2 was significantly lower in the OPD group (OPD: 92 ± 16; Control: 140 ± 31; p<0.05) and % vascular area/ total area evaluated showed no significant difference (OPD: 15.6 ± 6.1; Control: 10.2 ± 4.2). Number of VEGF+ cells/mm2 was lower in the OPD group than in the control group, with statistically significant differences (OPD: 7804.8 ± 597; Control: 13187.6 ± 894; p<0.001). The results of this study suggest that monosodium olpadronate has an antiangiogenic effect. Further studies are needed to reveal its potential as an antitumor agent and its connection with the onset of BRONJ.

El factor de crecimiento vascular (VEGF) es una proteina que incrementa la permeabilidad vascular, induce la proliferacion, migracion y supervivencia de las celulas endoteliales. Los bifosfonatos (BFs) son drogas antirresortivas ampliamente utilizadas en el tratamiento de enfermedades que alteran el metabolismo oseo y de metastasis oseas. Desde el 2003 se han reportado casos de osteonecrosis de maxilar asociada al uso de BFs (ONAB). Escasas publicaciones explican los mecanismos que inducen la ONAB, algunos autores mencionan las alteraciones en la remodelacion osea y un cierto efecto antiangiogenico de los BFs. El objetivo del presente trabajo es evaluar la expresion de VEGF en celulas de la medula osea y el numero y el area ocupada por vasos sanguineos en animales tratados con el BF olpadronato monosodico (OPD). Se utilizaron 16 ratas Wistar de 60 dias divididas en dos grupos, experimental (OPD) y control. El grupo OPD, recibio 0,3 mg/kg/sem de OPD via IP, durante 5 semanas. El grupo control, recibio un volumen equivalente via IP de solucion fisiologica. Luego de practicada la eutanasia se obtuvieron las hemimandibulas y se procesaron para obtener cortes histologicos mesio-distales del primer molar. Se realizo la coloracion hematoxilina-eosina (HE) y la deteccion inmunohistoquimica de VEGF (sc-7269) y se evaluaron los siguientes parametros histomorfometricos: En cortes con H&E: Numero de vasos sanguineos por mm2 y porcentaje (%) de area ocupada por los vasos sanguineos en relacion al area total evaluada; en cortes con la deteccion inmunohistoquimica de VEGF: Numero de celulas medulares VEGF+ por mm2. Los datos fueron estadisticamente analizados. El N° vasos sanguineos/mm2 fue significativamente menor en el grupo OPD (OPD: 92 ± 16; control: 140 ± 31; p<0,05) y el % area vascular/area total evaluada no mostro diferencias significativas (OPD: 15,6 ± 6.1; Control: 10.2 ± 4.2). El N° de celulas VEGF+/mm2 en el grupo OPD fue menor que en el grupo control con diferencias estadisticamente significativas (OPD: 7804,8 ± 597; Control: 13187,6 ± 894; p<0,001). Los resultados de este estudio sugieren que el olpadronato monosodico tiene un efecto antiangiogenico. Futuros estudios revelaran su potencial como agente antitumoral asi como tambien su relacion con la aparicion de ONAB.

Evaluation of vascular endothelial growth factor (VEGF) in interradicular bone marrow in olpadronate treated animals.

UNLABELLED: Vascular endothelial growth factor (VEGF) is a protein that increases vascular permeability and induces the proliferation, migration and survival of endothelial cells. Bisphosphonates (BPs) are antiresorptive drugs that are widely used in the treatment of bone metabolism diseases and bone metastases. Since 2003, cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) have been reported. Few papers explain the mechanisms that induce BRONJ; some authors mention alterations in bone remodelling and a certain antiangiogenic effect of BPs. The aim of this study is to evaluate the expression of VEGF in bone marrow cells and the number of blood vessels and area occupied by them in animals treated with the BP sodium olpadronate (OPD). We used 16 Wistar rats, 60 days old, divided into two groups, experimental (OPD) and control. The OPD group received 0.3 mg/kg/week intraperitoneal OPD for 5 weeks. The control group received an equivalent intraperitoneal volume of physiological saline solution. After euthanasia, hemimandibles were processed and mesio-distal histological sections of the first molar were prepared. Sections were stained with hematoxylin-eosin (HE), immunohistochemical detection of VEGF was performed (sc-7269) and the following histomorphometric parameters were evaluated: In HE-stained sections--number of blood vessels per sq. mm. and percentage (%) of area occupied by blood vessels in relation to total area evaluated; in sections with immunohistochemical detection of VEGF--number of VEGF+ bone marrow cells per sq. mm. Data underwent statistical analysis. Number of blood vessels/mm2 was significantly lower in the OPD group (OPD: 92 +/- 16; CONTROL: 140 +/- 31; p < 0.05) and % vascular area/total area evaluated showed no significant difference (OPD: 15.6 +/- 6.1; CONTROL: 10.2 +/- 4.2). Number of VEGF+ cells/mm2 was lower in the OPD group than in the control group, with statistically significant differences (OPD: 7804.8 +/- 597; CONTROL: 13187.6 +/- 894; p < .001). The results of this study suggest that monosodium olpadronate has an antiangiogenic effect. Further studies are needed to reveal its potential as an antitumor agent and its connection with the onset of BRONJ.

Nicotine impairs distraction osteogenesis in the rat mandible.

Distraction osteogenesis (DO) has gained clinical acceptance as a surgical technique for treatment of congenital craniomaxillofacial deficiencies requiring skeletal expansion. The use of this technique elsewhere requires more information on overcoming difficult clinical settings, for which new animal models will be needed. The aim of this study was to develop and validate a model of impaired DO of the rat mandible with nicotine. Twenty rats underwent a right vertical mandibular body osteotomy, after which distraction began with custom-made percutaneous devices and a 3-day latency period, 6-day distraction (0.25 mm twice daily) and 30 days of neutral fixation. Rats received either nicotine or placebo slow-release pellets. Specimens were analysed after removal of the devices for quantitative radiographic bone fill, amount of bone advancement and histological features. The mean radiographic bone-fill score with nicotine treatment was 75% of that with placebo (P=0.0036). The nicotine-treated rats had less (49%) elongation than the placebo-treated controls (P=0.0008). Histological analysis demonstrated less bone, vascularity and cellular activity in nicotine-treated rats. This study shows that nicotine reproducibly inhibits osteogenesis, vascularity and bone lengthening in mandibular DO.

The effect of anabolic steroids on mandibular growth.

The aim of this study was to assess the effect of nandrolone (Deca-Durabolin, AKZO Nobel, Cambridge, United Kingdom) on mandibular growth in juvenile and adult rats with radiographic cephalometry and immunoradiology. Juvenile (n = 16) and adult (n = 16) inbred female Wistar-Kyoto rats were compared. Each group was divided into 2 subgroups with 8 experimental (E) and 8 control (C) animals in each subgroup. Lateral headfilms taken before and after the 70-day study period were analyzed. Body weight and blood serum IGF-I levels were monitored weekly. The results showed marked mandibular growth changes in both the juvenile and the adult E rats. Body weight increase was larger in the E than in the C animals. The IGF-I blood serum levels were similar in the juvenile E and C rats but higher in the adult E animals than in the adult C animals. It was found that the anabolic steroid (Deca-Durabolin) had a significant effect on mandibular growth in both juvenile and adult rats.

Enhancement by hepatocyte growth factor of bone and cartilage formation during embryonic mouse mandibular development in vitro.

To elucidate the possible roles of hepatocyte growth factor (HGF) in the early development of mouse mandible, HGF was applied to an organ-culture system with chemically defined media. Mandibular arches microdissected from mouse embryos at the 10th day of gestation were cultured for 10 days with or without HGF, HGF plus HGF-receptor (c-met) antisense oligodeoxyribonucleotide, or HGF plus c-met sense oligodeoxyribonucleotide in the media. The cultured mandibles were then analysed, histologically in serial paraffin sections. In the absence of HGF, the tooth organs of bud stage, Meckel's cartilage and the tongue were formed, whereas only a slight amount of bone tissue was formed in the cultured mandible. The expression of intrinsic HGF and c-met in the cultured mandibles was confirmed by reverse transcriptase-polymerase chain reaction. Furthermore, immunohistochemistry demonstrated that both HGF and c-met were localized in areas of the mesenchymal tissue forming bone and cartilage. With HGF in the medium, the volume of both bone and cartilage increased significantly and dose-dependently. HGF also increased the rate of proliferation of osteogenic cells and chondrocytes. Addition of c-met antisense oligodeoxyribonucleotide partially inhibited the HGF-induced enhancement of bone and cartilage formation, whereas addition of c-met sense oligodeoxyribonucleotide had no effect. These results revealed that exogenous HGF enhances bone and cartilage morphogenesis in the cultured mandibles, suggesting physiological roles for intrinsic HGF in the early development of mouse mandible.

Instruction by retinoic acid of incisor morphology in the mouse embryonic mandible.

Endogenous retinoids are present in the embryonic mouse mandible and reach a peak in concentration at the time of the formation of the dental lamina. All-trans retinoic acid is present in a 10-fold higher concentration in the future incisor region of the mouse embryonic mandible at day 11.5. It was found here that exogenous all-trans retinoic acid has pleiotropic effects on the pattern of odontogenesis when applied before the formation of the dental lamina. These effects include a change in the pattern of the dental lamina, supernumerary buds and incisors in the diastema region, and replacement of molars with incisors in the molar region. Thus retinoic acid appears to instruct incisor morphology in the mouse embryonic mandible.

Blockade of the initiation of murine odontogenesis in vitro by citral, an inhibitor of endogenous retinoic acid synthesis.

Endogenous retinoids are present in the embryonic mouse mandible and reach a concentration peak immediately before the formation of the dental lamina. Because exogenous retinoids alter the pattern of the dental lamina and the expression of epidermal growth factor mRNA (a transcript necessary for initiation of odontogenesis), the role of retinoic acid in the initiation of odontogenesis was studied here. Citral (3,7-dimethyl-2,6-octadienal), a known inhibitor of retinoic acid synthesis, was used to block the endogenous synthesis of retinoic acid in the mouse embryonic mandible before the formation of the dental lamina (gestational day 9). A 24-h exposure to citral totally blocked tooth formation in 7/10 mandibles. Reductions of endogenous retinoic acid concentrations were confirmed by high-performance liquid chromatography. Tooth formation was restored by simultaneous treatment with all-trans retinoic acid or 9-cis retinoic acid during the citral exposures (first 24 h of culture). Endogenous retinoic acid is necessary for the initiation of odontogenesis.

Arch dimensional changes in children with idiopathic short stature treated with recombinant growth hormone: a five-year study.

Recombinant human growth hormone (rhGH) increases stature when administered to non-GH-deficient idiopathic short statured children. The aims of this investigation were to determine pretreatment arch dimensions of short statured children (height > or = 2 S.D. below mean for age) and to evaluate their response to rhGH administration by measuring arch-dimensional changes over 5 years of rhGH treatment. Dental casts of 28 short subjects (22 male, 6 female) and of age/gender-matched controls of normal stature were analyzed using a digital imaging system. Four measures of arch width and one of arch depth were calculated for each maxillary and mandibular cast. Subjects receiving orthodontic care were eliminated from the study at the initiation of treatment. Z-scores were calculated to allow for pooling of data. Prior to rhGH treatment, all arch dimensions of the short statured subjects were smaller than the controls, with the exception of mandibular arch depth. Arch dimensions of the rhGH subjects did increase with the continued administration of rhGH. The control group also showed a significant trend for the arch dimensions to increase over time. The influence of rhGH treatment on arch dimensional changes over time remains equivocal based on the results of this investigation.

Effects of prenatal exposure to tobacco smoke on developmental stability in children.

The effects of maternal and paternal smoking on fetal and neonatal dental development were investigated in a sample of 199 school children. Fluctuating asymmetry was evaluated in the maxillary arcades of four groups of children: those whose mothers had smoked, those whose fathers had smoked, those whose parents both had smoked, and finally, those whose parents had not smoked. When the magnitudes of fluctuating asymmetry in children exposed to parental tobacco smoke from one parent only were compared with the control group, no general univariate differences were found. Children exposed to smoke from both parents, however, showed significantly elevated levels of asymmetry in four out of six comparisons. In contrast, an analysis of variance failed to find significant differences on the basis of sex, parity, smoking status, or their interactions. It is concluded that parental smoking does not result in developmental destabilization of the fetus and neonate.

Histologic changes in dental morphology induced by high dose chemotherapy and total body irradiation.

Disturbances in dental development were studied with the use of radiography and histology in a patient with acute lymphoblastic leukemia who was treated with induction chemotherapy at 2.3 years of age and bone marrow transplantation at 4.3 years of age. The follow-up 9.5 years after bone marrow transplantation showed evidence of short tapered roots, enamel hypoplasia, microdontia, and aplasia. A histologic examination of two extracted permanent teeth showed that the crown of the maxillary lateral incisor exhibited numerous incremental lines that corresponded closely to the treatment periods with cytotoxic drugs. The maxillary second premolar exhibited regularly spaced incremental lines in the enamel and dentine. A gross hypoplasia was seen in the cervical part of the crown corresponding to the time of administration of 10 Gy total body irradiation. The results indicate that chemotherapy mainly induces qualitative disturbances in dentine and enamel, whereas total body irradiation induces both qualitative and quantitative changes.

Anabolic steroid abuse and tooth size-arch dimensions in the rat.

Anabolic steroids are misused by adolescents and adults to increase muscle mass and improve appearance and athletic performance. Since anabolics strongly enhance protein synthesis, it was speculated that alterations in tooth size and arch length could occur. This study quantified the effects of the anabolic steroid nandrolone phenpropionate on these parameters in a rat model. The steroid significantly increased mandibular arch length. No difference in mesiodistal dimensions of the molars occurred. In consequence, the increased arch dimensions combined with unaltered tooth size may result in dental spacing and/or other malocclusions.