A combination of ascorbic acid and α-tocopherol to test the effectiveness and safety in the fragile X syndrome: study protocol for a phase II, randomized, placebo-controlled trial

BACKGROUND: Fragile X syndrome (FXS) is an inherited neurodevelopmental condition characterised by behavioural, learning disabilities, phisical and neurological symptoms. In addition, an important degree of comorbidity with autism is also present. Considered a rare disorder affecting both genders, it first becomes apparent during childhood with displays of language delay and behavioural symptoms. Main aim: To show whether the combination of 10 mg/kg/day of ascorbic acid (vitamin C) and 10 mg/kg/day of α-tocopherol (vitamin E) reduces FXS symptoms among male patients ages 6 to 18 years compared to placebo treatment, as measured on the standardized rating scales at baseline, and after 12 and 24 weeks of treatment. Secondary aims: To assess the safety of the treatment. To describe behavioural and cognitive changes revealed by the Developmental Behaviour Checklist Short Form (DBC-P24) and the Wechsler Intelligence Scale for Children–Revised. To describe metabolic changes revealed by blood analysis. To measure treatment impact at home and in an academic environment. METHODS/DESIGN: A phase II randomized, double-blind pilot clinical trial. Scope: male children and adolescents diagnosed with FXS, in accordance with a standardized molecular biology test, who met all the inclusion criteria and none of the exclusion criteria. Instrumentation: clinical data, blood analysis, Wechsler Intelligence Scale for Children–Revised, Conners parent and teacher rating scale scores and the DBC-P24 results will be obtained at the baseline (t0). Follow up examinations will take place at 12 weeks (t1) and 24 weeks (t2) of treatment. DISCUSSION: A limited number of clinical trials have been carried out on children with FXS, but more are necessary as current treatment possibilities are insufficient and often provoke side effects. In the present study, we sought to overcome possible methodological problems by conducting a phase II pilot study in order to calculate the relevant statistical parameters and determine the safety of the proposed treatment. The results will provide evidence to improve hyperactivity control and reduce behavioural and learning problems using ascorbic acid (vitamin C) and α-tocopherol (vitamin E). The study protocol was approved by the Regional Government Committee for Clinical Trials in Andalusia and the Spanish agency for drugs and health products. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01329770 (29 March 2011

Bone remodelling after regenerative procedures around implants placed in fresh extraction sockets: an experimental study in Beagle dogs.

Abstract INTRODUCTION: After a tooth extraction, the height of the buccal wall tends to decrease. The literature indicates that regenerative techniques (guided bone regenerative [GBR] techniques) have succeeded in improving the bone levels. Therefore, this experiment set out to compare the physiological bone remodelling in Beagle dog models after implant placement in a fresh extraction socket, with and without the application of regenerative procedure. MATERIALS AND METHODS: Five dogs were used in this study. Test and control sites were randomly selected. The experimental teeth (fourth pre-molar and first molar) were hemi-sected removing the distal roots and placing implants. Porcine bone was placed to fill the gap around the implant on the test sites and a reabsorbable membrane was used to cover the area. The dogs were put down at different times (2 weeks, 1 month and 3 months). The measurements were taken immediately and at 2, 4, 12 weeks after implant placement. Student's test for paired data was used to compare the means of the clinical measurements. RESULTS: At 2 weeks: On the control sites, few signs of resorption were detected at the first molar only, while at the test sites bone levels were placed at the implant shoulder or above. At 4 weeks: On the control site, slight bone remodelling was observed, while on the test site minor signs of resorption or an increase of bone levels were detected. At 12 weeks: The alveolar crest on the control sites showed various degrees of remodelling. On the test sites stable bone levels or an increase of bone crest was observed. CONCLUSION: With the limits of this study, the findings showed that GBR techniques were able to limit resorption of the alveolar crest after tooth extraction. A pattern of bone remodelling after tooth extraction and implant placement was observed in the control sites (no GBR) as well as in test sites (GBR), and although the exact cause of this is unclear, surgical trauma could play a role. Further studies are necessary to confirm these results and to clarify the precise causes of bone remodelling in fresh extraction sockets

Bone Remodelling around Implants Placed in Fresh Extraction Sockets

The aim of the present experimental study was to evaluate the physiologic bone remodeling in beagle dogs following the placement of small-diameter (3.25 mm) implants in fresh extraction sites. Five 1-year-old beagle dogs that weighed approximately 10 to 13 kg each were used in this study. The third and fourth premolars (P3, P4) were used as experimental teeth, which were hemisected using a fissure bur; the distal roots were removed carefully using forceps. Implants (3.25-mm wide, 10- or 11.5-mm long) were placed in the fresh extraction sockets with the neck of the implant at the level of the buccal bone crest. The dogs were subsequently put to sleep according to the following schedule: one dog 15 days after implant placement, two dogs after 1 month, and the remaining two dogs after 3 months. The distance from the implant shoulder to the bone wall crest was measured at both the buccal and lingual sites. The width of the buccolingual bone crest was measured using a caliper. Assessments were made immediately after root extraction and at 2, 4, and 12 weeks after implant placement. The mean width of the buccolingual bone crest was 4.5 ± 0.5 mm at the time of root extraction. Subsequently, at 2, 4, and 12 weeks after implant placement, the buccolingual bone width was 4.1 ± 0.5 mm, 3.7 ± 0.3 mm, and 3.5 ± 0.7 mm, respectively. Two weeks after implant placement, the lingual bone crest was measured at 0.2 ± 0.3 mm from the implant shoulder, while the buccal bone crest was 0.3 ± 0.3 mm. After 4 weeks of healing, the mean distance from the implant shoulder to the lingual bone crest was 0.1 ± 0.9 mm, compared to 0.4 ± 0.9 mm for the buccal bone crest. After 12 weeks of healing, the bone crest at the lingual sites was -0.3 ± 0.5 mm from the implant shoulder, compared to 0.8 ± 0.3 mm at the buccal sites. The findings from this study show that although vertical bone remodeling was indeed observed, the mean vertical buccal bone resorption was 0.5 mm. It might be suggested, therefore, that the implant position along the lingual wall and the use of implants with a narrow diameter in relation to the extraction socket width play a key role in reducing the rate of vertical bone resorption at the buccal aspect of implants placed in fresh extraction sockets

Tilted implants for the restoration of posterior mandibles with horizontal atrophy: An alternative treatment

Purpose: Horizontal atrophy in the posterior mandible presents serious limitations on conventional implant placement. The purpose of this study was to evaluate the use of tilted implants angled in a buccolingual direction for restoring atrophic posterior mandibular sectors. Materials and Methods: A cohort study was performed of 25 patients who had partial prostheses supported by more than 1 implant ($1 tilted and 1 axial implant) to restore molar areas in the mandible. When the bone thickness was at least 5 mm, axial implants were placed; when the alveolar ridge was narrower, the implant was placed with tilted angulation. The beds for these tilted implants were prepared using a lingual approach, tipping the implant apex toward the vestibule. Twelve months after loading, bone loss was evaluated and the success rates of the tilted and axial implants were calculated. Results: The study included 20 women and 5 men (mean age, 54.8 yr) who received 67 implants in the posterior mandibular sectors. Thirty-nine implants were placed with a buccal angulation and 28 implants were placed vertically. Mean bone losses of 0.59 0.26 mm among the tilted implants and 0.48 0.34 mm among the axial implants were observed 1 year after loading. The success rate of the tilted implants was 94.9%, and that of the axial implants was 100%. No significant differences in success rates or in bone loss between the tilted and axial implants were found at 12 months after loading. Conclusions: Twelve months after loading, tilted implants provided good results for the restoration of posterior mandibles with horizontal atrophy and no significant differences in success rates or marginal bone loss between tilted and axial implants were observed

Volumetric analysis of remodelling pattern after ridge preservation comparing use of two types of xenografts. A multi centre randomized clinical trial

OBJECTIVES: The aim of this randomized clinical trial was to analyse and compare the volumetric changes after ridge preservation procedures using two different biomaterials and to evaluate associations between outcome variables and pristine three-dimensional aspects of the ridges. MATERIALS AND METHODS: Twenty-eight patients subjected to single-tooth alveolar ridge preservation were enrolled in the present multicentre, single-blind, prospective and randomized clinical trial. Fourteen sites were randomly allocated to each experimental group. The experimental sites were grafted with pre-hydrated collagenated cortico-cancellous porcine bone (coll group) or with a cortical porcine bone (cort group) and a collagen membrane; a secondary soft tissue healing was obtained for all experimental sites. Plaster casts were scanned (preoperative, at 1 and 3 months postoperative). Analysis of volumes and areas was performed, and all measured variables were statistically compared. RESULTS: Intragroup analyses at 3 months revealed that when examining changes related to three-dimensional features of remodelling patterns (volume, surfaces, height and shape), the two biomaterials showed similar behaviours with a minor loss in volume and ridge surface. Intergroup analysis at 3-month survey revealed that volume resorption of the coll group (244 mm3 ) was significantly lower (P = 0.0140) than that of the cort group (349 mm3 ). The reduction for basal surface appeared significantly different between the two groups at 1-month survey only (P = 0.0137), while the final basal surface reduction was 4.9 and 12.2 mm2 for coll and cort group, respectively. The superior surface reduction was 40.8 mm2 for coll and 50.7 mm2 for cort group, with no significant difference between the two groups. CONCLUSION: At the 3rd month analysis, coll group showed a significantly lower reduction of ridge volume and a significantly smaller shrinkage of the basal area when compared to the cort group; moreover, the coll group experienced a smaller superior surface shrinkage when compared to the cort group, even though no significance was evaluated

Melatonin plus porcine bone on discrete calcium deposit implant surface stimulates osteointegration in dental implants

The aim of this study was to evaluate the effect of the topical application of melatonin mixed with collagenized porcine bone to accelerate the osteointegration on the rough discrete calcium deposit (DCD) surface implants in Beagle dogs 3 months after their insertion. In preparation for subsequent insertion of dental implants, lower premolars and molars were extracted from 12 Beagle dogs. Each mandible received three parallel wall implants with discrete calcium deposit (DCD) surface of 4 mm in diameter and 10 mm in length. The implants were randomly assigned to the distal sites on each side of the mandible in three groups: group I implants alone, group II implants with melatonin and group III implants with melatonin and porcine bone. Prior to implanting, 5 mg lyophylized powdered melatonin was applied to one bone hole at each side of the mandible. None was applied at the control sites. Ten histological sections per implant were obtained for histomorphometric studies. After a 4-wk treatment period, melatonin significantly increased the perimeter of bone that was in direct contact with the treated implants (P < 0.0001), bone density (P < 0.0001), new bone formation (P < 0.0001) in comparison with control implants. Topical application of melatonin on DCD surface may act as a biomimetic agent in the placement of endo-osseous dental implants and enhance the osteointegration. Melatonin combined with porcine bone on DCD implants reveals more bone to implant contact at 12 wk (84.5 +/- 1.5%) compared with melatonin treated (75.1 +/- 1.4%) and nonmelatonin treated surface implants (64 +/- 1.4%)