Clinical and radiographic performance of self-locking conical connection implants in the posterior mandible: Five-year results of a two-centre prospective study.

OBJECTIVE: This prospective study aims to assess the 5-year clinical performance of implants with internal conical connection and platform-switched abutments in the posterior mandible. MATERIAL AND METHODS: Healthy adults missing at least two teeth in the posterior mandible and with a natural tooth mesial to the implant site received two or three adjacent implants. After a transmucosal healing period single crown restorations were cemented on platform-switched abutments. Changes in marginal bone levels were investigated in standardized periapical radiographs from surgery and loading (baseline) to 60-months post-loading. RESULTS: Twenty-four patients received 52 implants. Bone remodelling took place between surgery and loading (mean:-0.5, SD:±0.4 mm). From loading to 60 months, there was a mean bone change of 0.27 (SD:±0.47 mm) which stabilized 24 months after prosthesis delivery (mean:0.2, SD:±0.46 mm). 71.7% of all implants presented bone preservation at 60 months irrespective of the initial insertion depth. Two implants were lost after 5 years and the success rate was 95.1%. Patient enquiry revealed high satisfaction. CONCLUSION: Internal conical connection implants with platform-switched abutments presented a high success rate and preservation of marginal bone levels at the implant shoulder after 5 years of loading.

Peri-implant defect grafting with autogenous bone or bone graft material in immediate implant placement in molar extraction sites-1- to 3-year results of a prospective randomized study.

OBJECTIVES: To evaluate the survival rate, the orobuccal bone resorption and stability of peri-implant hard and soft tissues following immediate implant placement of wide diameter implants in molar extraction sites and peri-implant defect grafting with autogenous bone (AB) or biphasic bone graft material (BBGM) with 1- to 3-year follow-up examinations. MATERIAL AND METHODS: Fifty wide diameter implants were placed in 50 patients immediately into molar extraction sockets by a flapless approach. Peri-implant defect augmentation was performed randomized with either AB or BBGM. Primary outcome variable was implant survival. Marginal bone level changes, orobuccal width of the alveolar crest, probing depths, and implant success were considered as secondary parameters. RESULTS: One implant of the BBGM group was lost, 1 patient withdrew from the study (drop-out). The remaining 48 patients were still in function at a follow-up period up to 31 months after implant insertion. Interproximal marginal bone level regenerated from -7.5 mm to the level of the implant shoulder (AB + 0.38 mm, BBGM + 0.1 mm) at final follow-up. The width of the alveolar crest changed by -0.08 mm (AB) and +0.72 mm (BBGM) at 1 mm, -0.36 mm (AB) and +0.27 mm (BBGM) at 3 mm, -0.36 mm (AB) and +0.31 mm (BBGM) at 6 mm apical to implant shoulder level. Success rate was 87.5% in the AB and 56.3% in the BBGM group (p = .058). CONCLUSIONS: Medium-term results prove a high survival rate, a favorable amount of bone generation in both groups and a low amount of orobuccal resorption in immediate molar implant insertion.

Peri-implant marginal bone loss reduction with platform-switching components: 5-Year post-loading results of an equivalence randomized clinical trial.

AIM: To compare the clinical performance and marginal bone levels of implants restored with platform-switching (PS) or platform-matching (PM) abutments. MATERIALS AND METHODS: Adult patients missing two or more adjacent teeth in the posterior mandible received 2-4 CAMLOG SCREW-LINE implants and were randomly allocated to the PM or PS group, receiving the corresponding prosthetic components from surgery onwards. Implants were conventionally loaded with single cemented crowns. Patients were followed annually for 5 years. Outcome measures were marginal bone level changes, implant survival, performance of the prosthetic components and clinical parameters plaque index, sulcus bleeding index and pocket probing depth. RESULTS: Thirty-three patients received 72 implants in the PM group, and thirty-five patients received 74 implants in the PS group. Sixty patients attended the final appointment, 31 had received PS components and 29 had received PM components with 65 and 63 implants, respectively. Global survival rate was 96.6% with no differences between groups (p = 0.647). After 5 years of functional loading, PS restored implants presented 0.23mm (95% CI: [0.03, 0.43], p = 0.025) lower marginal bone level changes. The two groups were declared non-equivalent. CONCLUSION: Patients requiring implant supported restorations in healed bounded or free end edentulous gaps of the mandible benefit from the use of PS components in terms of peri-implant marginal bone level maintenance, though it may not be clinically noticeable.

Immediate and flapless implant insertion and provisionalization using autogenous bone grafts in the esthetic zone: 5-year results.

OBJECTIVES: As the 2-year results for immediately inserted and provisionalized implants have been reported, it remained an open issue, whether the initially high success rates and the esthetic outcome remain stable for longer observation periods. Therefore, this prospective study examines the 5-year hard and soft tissue changes at implants placed in the anterior maxilla. MATERIAL AND METHODS: Meanwhile, 37 microthreaded implants were placed in 21 patients into extraction sockets with and without facial bone deficiencies by a flapless approach. Facial gaps and bony defects were grafted with autogenous bone chips. The implants were immediately provisionalized. The primary outcome parameters were the interproximal marginal bone level and the thickness of the facial bony wall. Implant success and Pink Esthetic Score (PES) were considered as secondary outcome parameters. RESULTS: Two patients with four implants withdrew from the study (dropouts), and the remaining 33 implants were still in function at a follow-up period of 68 months. Marginal bone height averaged 0.04 mm coronal to the implant shoulder. The thickness of the facial bony lamellae increased significantly between pre-op examination and 1-year follow-up (p = .002) and thereafter remained stable. Within 5 years of follow-up, 24 of 33 implants were clinically stable, free of signs and symptoms, and showed bone loss less than 1 mm. The mean PES ratings improved slightly from 10.7 pre-operatively to 11.7 at the last follow-up (p = .02). CONCLUSIONS: Interproximal marginal bone levels, survival rates, and esthetic results remain stable at the 5-year follow-up in implants used in an immediate insertion, reconstruction, and provisionalization concept. Facial marginal bone levels decreased slightly; however, this reduction did not affect the PES so far.

Immediate provisionalization in the esthetic zone: 1-year interim results from a prospective single-cohort multicenter study evaluating 3.0-mm-diameter tapered implants.

OBJECTIVES: The aim of this interim analysis of a 5-year prospective multicenter study is to evaluate clinical and radiological performance of immediately provisionalized 3.0-mm-diameter tapered implants. MATERIALS AND METHODS: Patients needing implant rehabilitation of maxillary lateral incisors or mandibular lateral and central incisors were treated with 3.0-mm-diameter implants placed in extraction or healed sites and immediately provisionalized. Clinical and radiographic examinations were performed at implant insertion, 6 months thereafter, and are ongoing. Marginal bone levels and changes, complications, the papilla, plaque, and bleeding indices, and the pink esthetic score (PES) were evaluated at each follow-up visit. RESULTS: Of 112 enrolled patients, 77 patients (91 implants) met the inclusion criteria. Seventy-one patients with 82 implants completed the 1-year follow-up. Three implants failed yielding a CSR of 96.7%. All failures occurred within the first 3 months after implant insertion. Marginal bone level changes from insertion to 6 months was - 0.57 ± 1.30 mm (n = 75) and from insertion to 12 months - 0.25 ± 1.38 mm (n = 72). Fifteen non-serious complications were recorded. Papilla index score and PES improved at the 1-year follow-up. Plaque formation and bleeding-on-probing showed no statistically significant differences between the 6-month and the 1-year visit. CONCLUSIONS: This 1-year analysis demonstrated high survival, stable bone levels, and healthy soft tissue with 3.0-mm-diameter implants. CLINICAL IMPLICATIONS: Narrow diameter implants are a safe and predictable treatment option in patients with limited bone volume and/or limited interdental space and eligible for immediate loading protocols.

Effect of platform switching on crestal bone levels around implants in the posterior mandible: 3 years results from a multicentre randomized clinical trial.

OBJECTIVE: Evaluation of differences in the clinical performance and crestal bone levels between implants restored with single crowns with platform-matched or platform-switched abutments after 3 years. MATERIAL AND METHODS: The study enrolled adult patients missing two or more adjacent teeth in the posterior mandible with natural teeth mesial to the implant site. Randomization followed open-flap implant insertion and the corresponding matching or switching healing abutments placed at surgery. Conventional loading was made with cemented crowns. Clinical follow-up took place annually after loading up to 3 years. Bone level changes were measured in standardized radiographs as the variation in crestal bone from one evaluation to the next. RESULTS: Sixty-three patients with a total of 135 implants (66 platform matching, 69 platform switching) were analysed. From surgery to 36 months, mean bone loss was 0.28 ± 0.56 mm for the platform-switching group and 0.68 ± 0.64 mm for the platform-matching group. A statistically significant difference was found between groups (p = 0.002) with an estimate of 0.39 mm (0.15-0.64, 95% CI) in favour of platform switching. CONCLUSIONS: After 3 years, platform-switching restorations showed a significant effect in the preservation of marginal bone levels compared to platform-matching restorations.

Immediately provisionalized OsseoSpeed(™) Profile implants inserted into extraction sockets: 3-year results.

OBJECTIVES: A sloped shoulder might improve the congruence between extraction socket and dental implant and may add to a better circumferential support of the peri-implant structures. Therefore, this study evaluates the 3-year clinical outcome (survival and success rates, marginal bone levels, and Pink Esthetic Score (PES)) of immediately inserted and provisionalized OsseoSpeed(™) Profile implants in the anterior maxilla. MATERIAL AND METHODS: Twenty-one implants were inserted in 16 patients. All implants were immediately placed into extraction sites with and without facial bone deficiencies. A flapless procedure was utilized, and the implants were provisionalized immediately. Facial gaps were grafted with autogenous bone chips from the mandibular ramus. Implant survival and success, the interproximal bone levels, the thickness of the facial bony wall, and the PES were evaluated. RESULTS: After a mean follow-up period of 43 months, 19 implants were still in function. One patient with 1 implant did not follow the study protocol (dropout) and 1 implant was lost at 10 weeks. Interproximal marginal bone levels measured -0.2 ± 0.4 mm (range, -1.0-0.4 mm) apical to the implant shoulder. The mean PES ratings were 11.9 ± 1.4 (range, 8-14) at the final examination. CONCLUSIONS: Clinical and radiographic results provide evidence that sloped implants can preserve the marginal bone circumferentially and are able to maintain soft tissue esthetics when inserted and provisionalized immediately, even in the presence of facial bony wall defects.

Radiographic evaluation of conical tapered platform-switched implants in the posterior mandible: 1-year results of a two-center prospective study.

OBJECTIVE: Long-term success of dental implants depends on healthy peri-implant soft tissues and adequate bone levels. This prospective study aims to assess bone level changes around implants with internal conical connection and platform-switching abutments in the posterior mandible. MATERIAL AND METHODS: Adult patients missing at least two teeth in the posterior mandible and with a natural tooth mesial to the implant site received two or three adjacent internal conical connection implants. After a minimum transmucosal healing period of 8 weeks, single crown restorations were cemented over platform-switching abutments. Changes in marginal bone levels were measured in standardized periapical radiographs from surgery and loading (baseline) to 12 months post-loading. RESULTS: Twenty-four patients received 52 implants. Bone remodeling took place between surgery and loading (-0.53 ± 0.40 mm). From loading to 12 months, there was a mean bone gain of 0.12 ± 0.42 mm which occurred mainly in the first 6 months after prosthesis delivery (0.11 ± 0.36 mm) and stabilized afterward. A total of 71.7% of all implants presented bone preservation or gain. No implant was lost at 1 year and the success rate was 100%. Patient inquiry revealed high satisfaction. CONCLUSION: Internal conical connection implants with platform-switching abutments presented high success rate and enhancement or preservation of marginal bone levels after 1 year of loading.

Platform switch versus platform match in the posterior mandible ­ 1-year results of a multicentre randomized clinical trial.

OBJECTIVE: The purpose of this ongoing randomized study was to assess differences in bone level changes and success rates using implants supporting single crowns in the posterior mandible either with platform matched or platform switched abutments. MATERIAL AND METHODS: Patients aged 18 and above, missing at least two teeth in the posterior mandible and with a natural tooth mesial to the most proximal implant site were enrolled. Randomization followed implant placement. Definitive restorations were placed after a minimum transgingival healing period of 8 weeks. Changes in crestal bone level from surgery and loading (baseline) to 12-month post-loading were radiographically measured. Implant survival and success were determined. RESULTS: Sixty-eight patients received 74 implants in the platform switching group and 72 in the other one. The difference of mean marginal bone level change from surgery to 12 months was significant between groups (p < 0.004). Radiographical mean bone gain or no bone loss from loading was noted for 67.1% of the platform switching and 49.2% of the platform matching implants. Implant success rates were 97.3% and 100%, respectively. CONCLUSIONS: Within the same implant system the platform switching concept showed a positive effect on marginal bone levels when compared with restorations with platform matching.

Maintenance of marginal bone support and soft tissue esthetics at immediately provisionalized OsseoSpeed implants placed into extraction sites: 2-year results.

BACKGROUND: Placement of implants into extraction sockets targets the maintenance of peri-implant hard and soft tissue structures and the support of a natural and esthetic contour. The main advantages of immediate implant insertion in comparison with delayed implant placement protocols are as follows: a reduced treatment time, less number of sessions, and, thus, the less invasive procedure. This study examines the clinical performance (survival rate, marginal bone levels and Pink Esthetic Score [PES]) of OsseoSpeed implants placed into extraction sockets with immediate provisionalization in the anterior maxilla after a follow-up of at least 12 months. METHODS: Twenty patients received a total number of 37 OsseoSpeed implants which were immediately inserted into extraction sockets with or without facial bone deficiencies of various dimensions. A flapless procedure was applied, and the implants were immediately provisionalized with temporary crowns without occlusal contacts. Facial gaps between implant surface and facial bone or the previous contour of the alveolar process were grafted with autogenous bone chips. Implants in diameters 3.5, 4.0, 4.5, and 5.0 with lengths of 11-17 mm were used in the study. During the course of the study, interproximal marginal bone levels, the thickness of the facial bony wall, implant success rate according to the criteria established by Buser, and the PES were assessed per implant. RESULTS: One patient with three implants did not continue the study after prosthesis delivery, the remaining 34 implants were still in function at the final follow-up (survival rate: 100%). The mean follow-up period was 27 months (range, 12-40 months). Marginal bone height at the level of the implant shoulder averaged -0.1 ± 0.55 mm (range, -1.25 to 1.47 mm) at the final follow-up. The mean PES ratings were 11.3 ± 1.8 (range, 6-14) at the final follow-up. In 78% of the patients, the PES was preserved or even improved. CONCLUSIONS: Success rates, marginal bone levels, and esthetic results suggest proof of principle for the preservation of marginal bone height at immediately placed and provisionalized OsseoSpeed implants after a follow-up of at least 12 months. Even implant sites with facial bony deficiencies can be successfully treated with a favorable esthetic outcome using the immediate implant insertion, immediate reconstruction, and immediate provisionalization technique.

Modification of xenogenic bone substitute materials--effects on the early healing cascade in vitro.

INTRODUCTION: Initial platelet activation with subsequent cytokine release at the defect site plays a crucial role in tissue integration. The aim of this study was to evaluate the influence of topographic and biomimetic collagen modifications of a xenogenic bone substitute material (BSM) on in vitro platelet activation and cytokine release. MATERIAL AND METHODS: Three types of xenogenic BSM were used. Two BSM with different levels of granularity (large granule BSM [XBSM/L], small granule BSM [XBSM/S]) and a BSM with collagen (XBSM/C). All three samples were incubated with platelet concentrate of four healthy volunteers at room temperature for 15 min. For all groups, highly thrombogenic collagen type 1 served as a reference and an additional preparation with platelet concentrate only (without XBSM) served as control. Platelet count and cytokine release of VEGF, PDGF, TGF-ß, and IGF into the supernatant were measured. RESULTS: Compared with the control group, XBSM/C showed an increase in platelets consumption (mean 41,000 ± 26,000/ml vs. 471,000 ± 38,000/ml), cytokine release of VEGF (mean 46.8 ± 7.2 pg/ml vs. 18.8 ± 2.7 pg/ml), and PDGF (mean 18,350 ± 795 pg/ml vs. 2726 ± 410 pg/ml) but not IGF (194,728 ± 51,608 pg/ml vs. 1,333,911 ± 35,314 pg/ml). There was also an increase in cytokine release of TGF-ß in XBSM/C compared with XBSM/S (77,188 ± 27,413 pg/ml vs. 38,648 ± 13,191 pg/ml), but no such difference when compared with XBSM/L (77,188 ± 27,413 pg/ml vs. 53,309 ± 29,430 pg/ml). XBSM/L showed higher platelets consumption (301,000 ± 45,000 vs. 415,000 ± 98,000) and a higher cytokine release of PDGF (3511 ± 247 pg/ml vs. 3165 ± 78 pg/ml) compared with XBSM/S. There was no distinct difference in the levels of VEGF, TGF-ß, and IGF between XBSM/L and XBSM/S. CONCLUSIONS: Topographic as well as biomimetic modifications of the xenogenic BSM showed an increased platelet activation and cytokine release in vitro. This effect on the intrinsic healing cascade could result in comparable enhanced soft- and hard-tissue regeneration in vivo.

Oral squamous cell carcinoma in the vicinity of dental implants.

OBJECTIVES: The study at hand presents a cohort of patients treated for carcinomas in the vicinity of dental implants for identification of potential risk factors. MATERIALS AND METHODS: The retrospective analysis covers patients treated for peri-implant carcinoma at our department between 1995 and 2011. An additional literature search focused likewise on peri-implant carcinomas. Obtained articles were screened for relevant risk factors and discussed in relation to our patient cohort. RESULTS: Fifteen patients were treated for peri-implant carcinoma. Six reported ongoing alcohol/tobacco consumption. Nine had a previously reported carcinoma of whom six had received radiotherapy after surgery. Time from implant placement until carcinoma diagnosis was 53.4 months on average. The literature search revealed 25 patients with peri-implant carcinoma and one with a sarcoma. Eight patients reported alcohol/tobacco consumption. Most patients exhibited risk factors for possible malignant transformation: previous carcinoma (n = 12), lichen (n = 4), irradiation (n = 3), and leukoplakia (n = 3). The average time until diagnosis was 51.6 months. CONCLUSIONS: Smoking, alcohol consumption, and the history of previous carcinoma characterize patients at risk for a peri-implant carcinoma. A balanced gender ratio might point at a higher risk for woman and additional risk factors promoting carcinogenesis apart from tobacco and alcohol consumption, a novel finding that has to be proven by larger patient counts. CLINICAL RELEVANCE: The incidence of carcinomas next to dental implants is low but may attain clinical relevance with raising implant figures worldwide. Patients at risk potentially profit from individualized recall intervals and careful evaluation.

Multiple resistance to betalactam antibiotics, azithromycin or moxifloxacin in implant associated bacteria.

BACKGROUND: Antibiotics are more and more frequently prescribed in dentistry for prevention and treatment of oral diseases. Bacterial resistance to these agents is clearly increasing, including even previously susceptible micro-organisms and true pathogens. The aim of the present investigation was to examine resistant bacterial strains with respect to possible multiple antibiotic resistance. METHODS: In a previous investigation, implant-associated bacteria were tested first as mixed cultures and again as pure isolates (n = 138) for resistance to one of five antibiotics (ampicillin/AM, ampicillin + sulbactam/AB, azithromycin/AZ, penicillin/PG, moxifloxacin/MX) using the Etest. The resistance of most of the pure isolates was lower than in mixed culture, but 31.2% had retained their original resistance. Subsequently, all 138 isolates were tested for resistance or susceptibility to the other four antibiotics, again using the Etest. RESULTS: 27.6% (38/138) of the isolates retained their original antibiotic resistance and were resistant to at least one other antibiotic (MIC > or = 128 microg/mL for AB, AM or AZ, > or = 32 microg/mL PG, > or = 24 microg/mL MX). 2.2% (3/138) strains had lost their original antibiotic resistance, but were resistant to at least one other antibiotic (MIC > 128 microg/mL for AB, AM, or AZ, > or = 32 microg/mL PG, > or = 24 microg/mL MX). CONCLUSIONS: Some of the isolates belonging to the implant-associated microflora were multi-resistant, even though the patients had not received any antibiotics six weeks prior to the sampling. The exact mechanisms that lead to multiple resistance need to be examined in further studies.

BMP-2 and bFGF release and in vitro effect on human osteoblasts after adsorption to bone grafts and biomaterials.

OBJECTIVES: Combination of scaffolds and growth factors is a promising option for several clinical problems in bone biomaterials. Simplified growth factor loading by adsorption from aqueous solution is one important option for this technology. We evaluated the adsorption followed by PBS rinsing, release and biological effect of transient loading with basic fibroblast growth factor (bFGF) and bone morphogenic protein 2 (BMP-2) on fresh frozen bone, processed bone matrix, collagen, and a ceramic material with immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and qRT-PCR. MATERIALS AND METHODS: The study consisted of three in vitro experiments (immunofluorescence, ELISA, and qRT-PCR) in human osteoblasts (HOB). The first evaluated the adsorption of the growth factors bFGF and BMP-2 to the biomaterials, analyzed by immunofluorescence assays. The second experiment used ELISA to analyze the release of the growth factors from the matrix. The biological effect of the growth factors on HOB was then studied with qRT-PCR experiments as the third step. RESULTS: Strongest sustained release peaks in ELISA were observed in bFGF loading on processed bone matrix (steam-resistant mineralized bone matrix, SMBM) with up to 553 pg/ml medium. BMP-2 loading was less effective in ELISA peak release experiments with up to 257 pg/ml medium in processed bone matrix (SMBM). bFGF showed also higher release peaks in collagen material (192 pg/ml) compared with BMP-2 (101 pg/ml). Cumulative release values 0-72 h were estimated. The expression of runX2, osteocalcin, and alkaline phosphatase as markers for osteoblast activity was correlating. CONCLUSION: The results showed sustained release of BMP-2 and bFGF after transient loading on bone biomaterials with a stronger effect in biological scaffolds. This is interesting for therapeutic growth factor loading as well as insights in natural growth factor matrix deposition during bone healing.

The original family revisited after 37 years: odontoma-dysphagia syndrome is most likely caused by a microduplication of chromosome 11q13.3, including the FGF3 and FGF4 genes.

OBJECTIVES: Fibroblast growth factors consist of receptor tyrosine kinase binding proteins involved in growth, differentiation, and regeneration of a variety of tissues of the head and neck. Their role in the development of teeth has been documented, and their presence in human odontogenic cysts and tumors has previously been investigated. Odontoma­dysphagia syndrome (OMIM 164330) is a very rare disorder characterized by clustering of teeth as compound odontoma, dysplasia and aplasia of teeth, slight craniofacial abnormalities, and dysphagia. We have followed the clinical course of the disease in a family over more than 30 years and have identified a genetic abnormality segregating with the disorder. MATERIALS AND METHODS: We evaluated clinical data from nine different family members and obtained venous blood probes for genetic studies from three family members (two affected and one unaffected). RESULTS: The present family with five patients in two generations has remained one out of only two known cases with this very rare syndrome. All those affected showed teeth dysplasia, oligodontia, and dysplasia and odontoma of the upper and lower jaw. Additional signs included dysphagia and strictures of the oesophagus. Comorbidity in one patient included aortic stenosis and coronary artery disease, requiring coronary bypasses and aortic valve replacement. Genome-wide SNP array analyses in three family members (two affected and one unaffected) revealed a microduplication of chromosome 11q13.3 spanning 355 kilobases (kb) and including two genes in full length, fibroblast growth factors 3 (FGF3) and 4 (FGF4). CONCLUSION: The microduplication identified in this family represents the most likely cause of the odontoma­dysphagia syndrome and implies that the syndrome is caused by a gain of function of the FGF3 and FGF4 genes. CLINICAL RELEVANCE: Mutations of FGF receptor genes can cause craniofacial syndromes such as odontoma­dysphagia syndrome. Following this train of thought, an evaluation of FGF gene family in sporadic odontoma could be worthwhile.

Case report: Noonan syndrome with multiple giant cell lesions and review of the literature.

Noonan syndrome with multiple giant cell lesions (NS/MGCL) was recently shown to be a phenotypic variation within the syndromes of the Ras/MAPK pathway and not an independent entity as previously thought. Here we report on a 13-year-old boy with a typical phenotype of NS including atrial septal defect, pulmonic stenosis, short stature, and combined pectus carinatum/excavatum, pronounced MGCL of both jaws, and a de novo mutation in PTPN11, c.236A>G (which predicts p.Q79R). Mutations in PTPN11 are the most frequent cause of NS and p.Q79R is a recurrent mutation in exon 3. Including this patient, 24 patients with molecularly confirmed NS, LEOPARD, or CFC/MGCL syndrome have been reported to date, of these 21 patients have PTPN11, SOS1, or RAF1 mutations and three have BRAF or MAP2K1 mutations, confirming that MGCL is a rare complication of the deregulated RAS/MAPK pathway. In all patients, the lesions of the mandible and to a lesser extent of the maxilla were first noted between ages 2 and 19 years (median 11 years), and were combined with enlargement of the jaws in 11/24 patients (46%). In this case and, with one exception (mutation not reported), all previous cases the NS/MGCL was caused by known mutations in the PTPN11, SOS1, RAF1, BRAF1, and MAP2K1 genes that were previously reported with RASopathies without MGCL.

Prognostic parameters contributing to palatal implant failures: a long-term survival analysis of 239 patients.

OBJECTIVE: To evaluate the demographic, radiological and therapeutic parameters that influence the overall clinical performance of palatal implants subjected to orthodontic loading. PATIENTS AND METHODS: The data of all patients who had received an orthodontic palatal implant for skeletal anchorage between January 1998 and December 2007 were reviewed retrospectively. The primary endpoint was the implant loss. The following parameters were assessed by univariate (log-rank test) and multivariate (Cox's regression) analysis: (a) age and gender, (b) vertical bone height along the prospective implant axis, (c) surgeon's experience and (d) implant type. RESULTS: Two-hundred and thirty-nine palatal implants were inserted in patients aged between 10 and 65 years. In all, 11/239 (4.6%) implants were lost: nine during the healing phase and two under functional loading. On univariate analysis, "surgeon's experience" was associated with a better implant survival and vice versa (P=0.0005; log-rank test). The significance of "surgeon's experience" was confirmed by Cox's regression analysis (P=0.001; Wald test). All other parameters had no impact on implant loss. CONCLUSIONS: The survival probability of palatal implants is not related to demographic and radiological parameters. Implant losses mainly occurred early in the healing phase of the palatal implant. According to our data, "surgeon's experience" is the cornerstone of palatal implant success.

Bone formation with a biphasic calcium phosphate combined with fibrin sealant in maxillary sinus floor elevation for delayed dental implant.

OBJECTIVES: The aim of this study was to evaluate the extent and quality of new bone 6 months after sinus lift with biphasic micro- and macroporous calcium phosphate combined with fibrin sealant (MBCP-FS) and the 1-year implant success rate in the augmented site. MATERIAL AND METHODS: MBCP-FS was applied to one sinus in 96 subjects requiring augmentation for delayed dental implant placement. In subjects who required bilateral lifts (N = 33), the MBCP-FS sinus was randomly selected; the contralateral sinus was grafted with autologous bone (mixed with Bio-Oss when harvested bone volume was insufficient. Panoramic views were taken periodically prior to and up to 18 months post-lift. Histomorphometric analysis was conducted on biopsies taken during implant placement 6 months after augmentation. Implant functionality and prosthesis success were assessed clinically 1 year after implant placement. RESULTS: In MBCP-FS sinuses, 20.6 ± 8.5% new, mainly lamellar bone was observed. Implants were placed as planned in 78/85 evaluable subjects (91.8%) 6 months after sinus lift. Graft heights remained stable 1 year after placement; 94.7% (142/150) of implants were functional. The amount and quality of new bone and implant success rates with MBCP-FS were similar to autologous bone graft (mixed with Bio-Oss in 30/31 evaluable subjects). MBCP-FS was safe and well-tolerated. CONCLUSIONS: MBCP-FS is safe and effective in sinus floor elevation for dental implant placement, supporting bone regeneration and with high 1-year implant success rates similar to autologous bone mixed with Bio-Oss.

Promotion of osteogenic cell response using quasicovalent immobilized fibronectin on titanium surfaces: introduction of a novel biomimetic layer system.

PURPOSE: Despite the undeniable potential of cell adhesion molecules such as fibronectin to support osteogenic cell responses and consecutive dental implant healing, the most beneficial mode of application onto titanium implant surfaces still requires investigation. Unspecific fibronectin adsorption on titanium dioxide (TiO(2)) surfaces can result in low-loading, high-desorption rates and protein-metal interactions with impaired biologic activity. The aim of the present study was to monitor the osteogenic cell responses (cell adhesion, proliferation, and differentiation) specifically to fibronectin biofunctionalized TiO(2). MATERIALS AND METHODS: An innovative biomimetic streptavidin-biotin layer system allows flexible, but stable, specific binding of biotinylated biomolecules such as fibronectin on TiO(2) surfaces. Transparent glass disks were sputtered with TiO(2). The biomimetic layer system was immobilized by self-assembly and consisted of silane, biotin-derivate, streptavidin, and biotinylated fibronectin (bFN). For the control group, unbiotinylated fibronectin was directly coated onto TiO(2). Early cell adhesion dynamics were quantified using automated processing of light microscopy images within the first 24 hours. Relative mRNA expression of integrin-ß1, cyclin D1, runt-related gene 2, alkaline phosphatase, and osteocalcin was obtained using quantitative real-time polymerase chain reactions 3 and 7 days after incubation. RESULTS: Although untreated TiO(2) preserved a rather immature osteogenic phenotype, both unbiotinylated fibronectin and bFN promoted osteogenic cell adhesion and cell differentiation. In particular, runt-related gene 2 expression was significantly promoted by bFN after 3 days. In contrast, cyclin D1 expression was decreased for unbiotinylated fibronectin and bFN after 7 days. CONCLUSIONS: The introduced biomimetic layer system contributes a coherent immobilization approach of adhesion molecules with promotion of osteogenic cell response in vitro.

Histological evaluation of maxillary sinus floor augmentation with recombinant human growth and differentiation factor-5-coated ß-tricalcium phosphate: results of a multicenter randomized clinical trial.

OBJECTIVES: The aim of this prospective, multicenter, randomized clinical trial was to evaluate histologically the outcome of maxillary sinus lift augmentation with a recombinant human growth and differentiation factor-5-coated ß-tricalcium phosphate (rhGDF-5/ß-TCP) or with a ß-TCP and autogenous bone (ß-TCP/AB) composite. MATERIAL AND METHODS: Thirty-one patients requiring unilateral maxillary sinus floor augmentation (residual alveolar bone height <5 mm) were randomly allocated in three treatment groups: (a) rhGDF-5/ß-TCP and a 3-month healing period, (b) rhGDF-5/ß-TCP and a 4-month healing period, and (c) ß-TCP and intra-oral corticocancellous autologous bone (at 1:1) and a 4-month healing period. Cylindrical biopsies were harvested by means of a trephine bur during implant site preparation and evaluated histologically and histometrically. RESULTS: One patient withdrew from the study before implant placement; 66 implants were inserted in the remaining 30 patients. Four out of 47 (8.5%) implants failed in patients treated with rhGDF-5/ß-TCP. The proportion of newly formed bone was similar among groups and averaged 31.4% (± 17%) in the rhGDF-5/ß-TCP/3-month healing group, 28% (± 15.5%) in the rhGDF-5/ß-TCP/4-month healing group, and 31.8% (± 17.9%) in the ß-TCP/AB group. The proportion of remaining ß-TCP averaged 12.6% (± 14.4%) in the rhGDF-5/b-TCP/3-month group, 6.6% (± 6.3%) in the rhGDF-5/b-TCP/4-month group, and 16.5% (± 12.3%) in the ß-TCP/AB group. The new bone was primarily woven and characterized by slender trabeculae and narrow osteoid zones, and in many instances bone was in contact with residual biomaterial particles. Presence of AB particle remnants was only trivial, while minimal amounts of inflammation were observed only in a few cases. CONCLUSION: Sinus augmentation with rhGDF-5/ß-TCP resulted in comparable amounts of new bone and of similar quality as those obtained with a ß-TCP/AB composite graft.