Publication Bias in Five Dental Implant Journals: An Observation from 2005 to 2009

Purpose: This study evaluated possible publication bias and its related factors in implant-related research over time. Materials and Methods: Articles published in Clinical Implant Dentistry and Related Research, Clinical Oral Implants Research, Implant Dentistry, Journal of Oral Implantology, and The International Journal of Oral & Maxillofacial Implants between 2005 and 2009 were reviewed. Nonoriginal articles were excluded. For each article included, study outcome, extramural funding source, type of study, and geographic origin were recorded. Descriptive and analytic statistics (alpha = .05), including the chi-square test and logistic regression analysis, were performed where appropriate. Results: From a total of 2,085 articles, 1,503 met the inclusion criteria. of the articles analyzed, 1,226 (81.6%), 160 (10.6%), and 117 (7.8%) articles reported positive, negative, and neutral outcomes, respectively. In vitro studies, studies from Asia, and funded animal studies were more likely to report positive outcomes compared to others (P = .02, P < .0001, and P = .009, respectively). Industry-funded studies represented the lowest frequency of positive outcomes versus studies funded by other sources. Conclusions: There were a high number of implant-related studies reporting positive outcomes in the five selected journals. Some selected factors were associated with positive outcome bias. In general, funding was not associated with a positive outcome, except for animal studies. Industry-supported research did not show any association with the publication of positive outcomes. INT J ORAL MAXILLOFAC IMPLANTS 2011;26:1024-1032

Trends in Funding, Internationalization, and Types of Study for Original Articles Published in Five Implant-Related Journals Between 2005 and 2009

Purpose: The aims of this study were to evaluate the trends in funding, geographic origin, and study types of original articles in the dental implant literature and to investigate the relationships among these factors. Materials and Methods: Articles published in Clinical Oral Implants Research, The International Journal of Oral & Maxillofacial Implants, Clinical Implant Dentistry and Related Research, Implant Dentistry, and Journal of Oral Implantology from 2005 to 2009 were reviewed. Nonoriginal articles were excluded. For each article included, extramural funding source, geographic origin, and study type were recorded. Descriptive and analytic analyses (alpha = .05), including a logistic regression analysis, and chi-square test were used where appropriate. Results: of a total of 2,085 articles published, 1,503 met the inclusion criteria. The most common source of funding was from industry (32.4%). The proportion of studies that reported funding increased significantly over time. Europe represented the highest percentage (55.8%) of published articles. Most of the articles reported on clinical studies (49.9%), followed by animal studies (25.9%). Articles from Asia and South America and animal and in vitro studies were significantly more likely to be funded. Conclusion: Almost half of the original dental implant articles were funded. The trend toward internationalization of authorship was evident. A strong association was observed between funding and geographic origin and between funding and study type. Most studies in North America and Europe were clinical studies and supported by industry, whereas a greater proportion of studies in Asia and South America were in vitro or animal studies funded through government resources. INT J ORAL MAXILLOFAC IMPLANTS 2012;27:69-76

Effect of cyclosporin A on alveolar bone homeostasis in a rat periodontitis model

Objectives: the administration of cyclosporin A has been associated with significant bone loss and increased bone remodeling. The present investigation was designed to evaluate the effects of cyclosporin A on alveolar bone of rats subjected to experimental periodontitis, using serum, stereometric and radiographic analysis.Methods: Twenty-four rats were divided into one of the following groups with six animals each: group I, control rats; group II, in which the animals received a cotton ligature around the lower first molars; group III, in which the rats received a cotton ligature around the lower first molars and were treated with 10 mg/(kg body weight day) of cyclosporin A; group IV, in which the rats were treated with 10 mg/(kg body weight day) of cyclosporin A. At the end of experimental period, at 30 days, animals were killed and the serum calcium and alkaline phosphatase levels were measured in all groups. The distance from the alveolar bone crest to the cemento-enamel junction was measured radiographically for each mesial surface of the lower first molars of each rat. After histological processing, the stereological parameters: volume densities of multinucleated osteoclasts (V-o), alveolar bone (V-b), marrow (V-m), and relation of eroded surface/bone surface (Es/Bs) were assessed at the mesial region of the alveolar bone.Results: Significant decreases in serum calcium were observed in those groups that received cyclosporin A therapy. No significant changes in serum alkaline phosphatase were observed. The therapy with cyclosporin A combined with the ligature placement decreased the V-b and increased the V-o, V-m and Es/Bs at the mesial surface of lower first molars. on the other hand, the radiographic data showed that cyclosporin A therapy diminished the alveolar bone loss at the mesial surface of the lower first molars.Conclusions: Therefore, within the limits of this study, we suggest that cyclosporin A at immunosuppressive levels can bring about an imbalance in the alveolar bone homeostasis in rats. However, in the presence of inflammatory stimulation, the inhibition of the immune system by cyclosporin A may decrease the initial periodontal breakdown.

Progression of experimental chronic peri-implantitis in dogs: Clinical and radiographic evaluation

Background: the aim of this study was to evaluate the progression of experimental peri-implantitis in dogs using implants with different surface coatings.Methods: Thirty-six dental implants with four different surface coatings, commercially pure titanium (cpTi), titanium plasma-sprayed (TPS), hydroxyapatite (HA), and acid-etched (AE), were placed in six mongrel dogs. Five months after implantation, peri-implantitis was induced by cotton ligatures to facilitate plaque accumulation for 60 days. After 60 days, the ligatures were removed and supragingival plaque control was initiated for 12 months. Probing depth (PD), clinical attachment level (CAL), vertical bone level (VBL), horizontal bone level (HBL), and mobility were obtained at baseline, and 20, 40, 60 (acute phase), and 425 days (chronic phase) after ligature removal.Results: PD and CAL changed around all implant surfaces after ligature placement (P < 0.0001). However, the means of PD and CAL were not statistically significant among the different surfaces (P > 0.05). The range of CAL variation, calculated between baseline and 60 days (acute phase) and between 60 and 425 days (chronic phase), decreased (P < 0.05). Bone loss increased during the entire experiment (P < 0.0001). The HA surface showed the greatest bone loss measurement (5.06 +/- 0.38 mm) and the TPS showed the smallest bone loss (4.27 +/- 0.62 mm). However, statistical significance was not assessed for different coatings (P > 0.05).Conclusions: the clinical data at the initial phase showed rapid and severe peri-implant tissue breakdown. However, removal of ligatures did not convert the acute destructive peri-implant phase to a non-aggressive lesion and the progression of peri-implantitis was observed at chronic phase. The,experimental peri-implantitis in dogs may be a useful model to evaluate the progression of peri-implantitis.

Regeneration of class III furcation defects with basic fibroblast growth factor (b-FGF) associated with GTR. A descriptive and histometric study in dogs

Background: the poor predictability of periodontal regenerative treatment of Class III furcation defects stimulates the study of alternatives to improve its results, such as the use of polypeptide growth factors. The objective of this study was to evaluate, both histologically and histometrically, the effects of topical application of basic fibroblast growth factor (b-FGF) associated with guided tissue regeneration (GTR) in the treatment of Class III defects surgically induced in dogs.Methods: All second and fourth premolars of 5 mongrel dogs were used and randomly assigned to one of three treatment groups: group 1 (control), treated with scaling and root planing, tetracycline hydrochloride (125 mg/ml) conditioning, and GTR with a collagen membrane; group 2, same treatment as group 1 plus 0.5 mg of b-FGF; group 3, same treatment as group 1 plus 1.0 mg of b-FGF. After a 90-day healing period, routine histologic processing and staining with hematoxylin and eosin and Masson trichrome were performed.Results: the descriptive analysis indicated better regenerative results in both groups treated with b-FGF while the histometric data, analyzed by means of analysis of variance (ANOVA), showed greater filling of the defects in group 2 in comparison to the defects in groups 3 and 1, respectively, which was represented by a smaller area of plaque-occupied space (P = 0.004) as well as a greater amount of newly formed cementum (P = 0.002).Conclusions: These results indicate that b-FGF, especially in smaller doses, may enhance the regenerative results in Class III furcation lesions, leading to greater filling of these defects with both mineralized and non-mineralized tissues.

The influence of loss of bone mass on induced periodontal disease: A radiographic and densitometric study of female rats

Background: Changes in mineral density in the mandibular and femoral bones (BMD) after estrogen deficiency caused by ovariectomy (OVX) and the influence of these changes on induced periodontal disease were evaluated in female rats.Methods: Forty-eight female Holtzman rats (90 days old) were randomly divided into five groups: 0: control (N = 9); 1: SHAM without induced periodontal disease (N = 11); 2: SHAM with induced disease (N = 10); 3: OVX without induced disease (N = 9); and 4: OVX with induced disease (N = 9). In groups 2 and 4, the first lower molars were tied with ligatures for 30 days 120 days after surgery. After 5 months the animals were sacrificed to measure global mineral density (BMD) and that of the sub-regions of the mandible and femur by dual energy x-ray absorptiometry (DXA). The extent of vertical bone loss was evaluated with digital radiography by measuring the distance from the bone crest to the cemento-enamel junction at the mesial of the first lower molar.Results: Results of the femur (Kruskal-Wallis test) showed a significant difference (P < 0.001) between the groups SHAM and OVX in bone density values for all regions. Comparison between the groups in relation to the BMD of the mandible, both in the sub-regions and global revealed no differences (P < 0.05). The vertical bone loss measured for the groups with induced disease was similar (P= 0.713).Conclusions: Differences between the groups were found in the bone mineral density BMD of the femur but not of the mandible. OVX had no influence on induced periodontal disease.

Clinical and radiographic changes around dental implants inserted in different levels in relation to the crestal bone, under different restoration protocols, in the dog model

Background: The aim of the present study was to evaluate clinical and radiographic changes that occur around dental implants inserted in different levels in relation to crestal bone under different restoration protocols.Methods: Thirty-six implants were inserted in the edentulous mandible of six mongrel dogs. Each implant was assigned to an experimental group according to the distance from the top of the implant to the crestal bone: Bone Level (at crestal bone level), Minus 1 (1 mm below crestal bone), or Minus 2 (2 mm below crestal bone). Each hemimandible was submitted to a restoration protocol: conventional (prosthesis was installed 120 days after implant placement, including 30 days with healing cap) or immediate (prosthesis was installed 24 hours after implant placement). Fixed partial prostheses were installed bilaterally in the same day. After 90 days, clinical and radiographic parameters were evaluated.Results: As long as the implants were inserted in more apical positions, the first bone-to-implant contact (fBIC) was positioned more apically (P<0.05). However, the apical positioning of the implants did not influence the ridge loss or the position of the soft tissue margin (PSTM) (P>0.05). In addition, in immediately restored sites, the PSTM was located significantly more coronally than that in conventionally restored sites (P=0.02).Conclusions: Despite the more apical positioning of the fBIC, the height of the peri-implant soft tissues and ridge was not jeopardized. Moreover, the immediate restoration protocol was beneficial to the maintenance of the PSTM. Further studies are suggested to evaluate the significance of these results in longer healing periods.

Effect of selective cyclooxygenase-2 inhibition on the development of ligature-induced periodontitis in rats

Background: the purpose of this study was to evaluate the effect of a selective cyclooxygenase-2 inhibitor on the progression of alveolar bone loss in an experimental periodontitis model in rats.Methods: One hundred eighty (180) Wistar rats were separated into 3 experimental groups. Cotton ligatures were placed at the gingival margin level of lower right first molars. The rats were randomly assigned to one of the following groups that received: a daily oral dose of 10 mg/kg body weight of celecoxib (Ce1); 20 mg/kg body weight of celecoxib (Ce2); or 10 ml/kg of saline solution (C). Serum levels of celecoxib and white blood cell count were determined. Standardized digital radiographs were taken after sacrifice at 3, 5, 10, 18, and 30 days to measure the amount of bone loss around the mesial root surface of the first molar tooth in each rat.Results: Two-way analysis of variance (ANOVA) indicated that groups treated with celecoxib had significantly less bone loss compared to controls (P <0.0001) and that there was a significant interaction between treatment with celecoxib and time (P <0.03). Post-hoc comparisons showed that in both groups treated with celecoxib, the bone loss became significant only after 10 days of ligature placement, while in the control group it was already significant after 5 days. However, differences in mean bone loss between control and Ce1 were significant only at 18 days and, between control and Ce2, at 5 and 18 days. There was no significant difference in bone loss among experimental groups at the end of the experimental period.Conclusion: These data provide evidence that systemic therapy with celecoxib can modify the progression of experimentally induced periodontitis in rats.

Determination of anaerobic threshold in rats using the lactate minimum test

The break point of the curve of blood lactate vs exercise load has been called anaerobic threshold (AT) and is considered to be an important indicator of endurance exercise capacity in human subjects. There are few studies of AT determination in animals. We describe a protocol for AT determination by the lactate minimum test in rats during swimming exercise. The test is based on the premise that during an incremental exercise test, and after a bout of maximal exercise, blood lactate decreases to a minimum and then increases again. This minimum value indicates the intensity of the AT. Adult male (90 days) Wistar rats adapted to swimming for 2 weeks were used. The initial state of lactic acidosis was obtained by making the animals jump into the water and swim while carrying a load equivalent to 50% of body weight for 6 min (30-s exercise interrupted by a 30-s rest). After a 9-min rest, blood was collected and the incremental swimming test was started. The test consisted of swimming while supporting loads of 4.5, 5.0, 5.5, 6.0 and 7.0% of body weight. Each exercise load lasted 5 min and was followed by a 30-s rest during which blood samples were taken. The blood lactate minimum was determined from a zero-gradient tangent to a spline function fitting the blood lactate vs workload curve. AT was estimated to be 4.95 ± 0.10% of body weight while interpolated blood lactate was 7.17 ± 0.16 mmol/l. These results suggest the application of AT determination in animal studies concerning metabolism during exercise.

The influence of chlorhexidine on the severity of cyclosporin A-induced gingival overgrowth

THE INFLUENCE OF CHEMICAL PLAQUE CONTROL, using topically applied 0.12% chlorhexidine, on the severity of cyclosporin A (CsA)-induced gingival overgrowth (GO) was evaluated. Forty Holtzman rats were divided into four groups: 1) control; 2) cyclosporin A: a 10mg/kg/day subcutaneous dose of CsA; 3) chlorhexidine: 0.12% chlorhexidine (CHX) was applied to the buccal surface of the right mandibular molars; and 4) cyclosporin A/chlorhexidine: a combination of the treatment described for cyclosporin A and chlorhexidine groups. The animals were fed a high sucrose diet during the experiment and were sacrificed after 14 and 21 days. The histometric analysis revealed a significant increase in buccal gingival area in the cyclosporin A group compared to other groups (P < 0.01) after 21 days. The epithelium thickness of the buccal gingiva was significantly increased in the cyclosporin A group, compared to the control group (P < 0.05). The cyclosporin A/chlorhexidine group exhibited statistically significantly lower gingival overgrowth than the cyclosporin A group. These findings, if replicated in human studies, suggest that topically applied 0.12% chlorhexidine may be a valuable measure in the management of cyclosporin-induced gingival overgrowth.

Treatment of ligature-induced peri-implantitis by lethal photosensitization and guided bone regeneration: A preliminary histologic study in dogs

Background: the purpose of this pilot study was to evaluate the healing potential and reosseointegration in ligature-induced peri-implantitis defects adjacent to various dental implant surfaces following lethal photosensitization.Methods: A total of 36 dental implants with 4 different surface coatings (9 commercially pure titanium surface [CPTi]; 9 titanium plasma-sprayed [TPS]; 9 hydroxyapatite [HA]; and 9 acid-etched [AE]) were inserted in 6 male mongrel dogs 3 months after extraction of mandibular premolars. After a 2-month period of ligature-induced peri-implantitis and 12 months of natural peri-implantitis progression, only 19 dental implants remained. The dogs underwent surgical debridement of the remaining dental implant sites and lethal photosensitization by combination of toluidine blue O (100 mug/ml) and irradiation with diode laser. All exposed dental implant surfaces and bone craters were meticulously cleaned by mechanical means, submitted to photodynamic therapy, and guided bone regeneration (GBR) using expanded polytetrafluoroethylene (ePTFE) membranes. Five months later, biopsies of the implant sites were dissected and prepared for ground sectioning and analysis.Results: the percentage of bone fill was HA: 48.28 +/- 15.00; TPS: 39.54 +/- 12.34; AE: 26.88 +/- 22.16; and CPTi: 26.70 +/- 16.50. The percentage of reosseointegration was TPS: 25.25 +/- 11.96; CPTi: 24.91 +/- 17.78; AE: 17.30 +/- 15.41; and HA: 15.83 +/- 9.64.Conclusion: These data suggest that lethal photosensitization may have potential in the treatment of peri-implantitis.

Healing of dehiscence defects following root surface demineralization with tetracycline: A histologic study in monkeys

Background: the purpose of this study was to histologically evaluate the healing of experimental dehiscence defects after surface demineralization with tetracycline hydrochloride.Methods: Six adult male monkeys (Cebus apella) were used in this study. Dehiscence defects were surgically created on the buccal aspect of the mandibular lateral incisors in all animals. The root surfaces were debrided and planed. In a split-mouth design, a 10% tetracycline hydrochloride solution was applied to one tooth for 4 minutes (T group), followed by irrigation with saline. The contralateral tooth served as a control (C group). The flaps were repositioned and sutured. The animals were sacrificed at 6 months postoperatively and histological sections were processed. Computer-assisted histomorphometric analysis was used to evaluate the formation of new cementum, new bone, new connective tissue attachment, and length of the epithelium (junctional and sulcular).Results: Bone regeneration was similar in both groups (1.5 +/- 0.3 mm for the T group and 1.5 +/- 0.6 mm for the C group). The C group showed more new cementum than the T group (2.3 +/- 0.3 mm versus 2.2 +/- 0.3 mm) as well as a longer epithelium (1.0 +/- 0.3 mm versus 0.9 +/- 0.2 mm). The T group presented more new connective tissue attachment (3.1 +/- 0.2 mm) than the C group (2.9 +/- 0.6 mm). However, no statistically significant differences were detected between the two groups.Conclusions: the amount of new attachment was similar in both groups. Root conditioning with 10% tetracycline solution did not produce any additional new attachment in comparison to the controls.

Influence of age on combined effects of cyclosporin and nifedipine on rat alveolar bone

Background: There is some evidence showing that cyclosporin A (CsA) and nifedipine (NIF) affect bone metabolism. The purpose of this work was to study the effects of CsA and NIF, given alone or concurrently, on alveolar bone of rats of different ages. Methods: Rats 15, 30, 60, and 90 days old were treated daily with 10 mg/kg body weight of CsA subcutaneously injected and/or 50 mg/kg body weight of NIF/day given orally for 60 days. Alveolar bone of the first lower molars was morphologically and stereologically evaluated in serial 5 μm bucco-lingual paraffin sections, stained with hematoxylin and eosin. Serum calcium and alkaline phosphatase levels were measured in all animals at the end of the experimental period. Results: Rats treated with CsA or NIF alone or CsA and NIF concurrently showed decreased alveolar bone density. CsA was more effective than NIF. A significant decrease in serum calcium was found only in animals treated with CsA or CsA/NIF. The results were similar regardless of age. Conclusions: These results indicate that the decrease in the alveolar bone volume in rats caused by CsA and NIF alone or concurrently is not age dependent. Furthermore, NIF (50 mg/kg) did not further increase the loss of alveolar bone volume induced by CsA (10 mg/kg).

Cyclosporin but not tacrolimus significantly increases salivary cytokine contents in rats

Background: Cyclosporin (CsA) and tacrolimus (FK-506) are immunosuppressive drugs that specifically inhibit T-cell activation via calcineurin inhibition. Gingival overgrowth is a common side effect following the administration of CsA. The severity of gingival overgrowth seen in patients taking FK-506 is less than that observed with CsA. Little is known about the involvement of saliva in drug-induced gingival overgrowth. The purpose of this study was to investigate the salivary contents of tumor growth factor β1 (TGF-β1), epidermal growth factor (EGF), and interleukin-6 (IL-6) as well as the hystometry of gingival tissue obtained from rats treated with either FK-506 or CsA. Methods: For 30 or 60 days rats received daily subcutaneous injection doses of either CsA or FK-506 (10 mg/kg). The concentrations of TGF-β1, EGF, and IL-6 in saliva were determined by enzyme-linked immunosorbent assay, and after histological processing, the oral epithelium and connective tissue were assessed at the region of the lower first molars. Results: The levels of TGF-β1, EGF, and IL-6 in saliva were not significantly altered by any of the treatments after 30 days. After 60 days of treatment with CsA, gingival overgrowth and significant increase in salivary TGF-β1, EGF, and IL-6 concentrations were observed; no statistically significant changes were induced by FK-506. Conclusion: Within the limits of this experimental study, it can be concluded that CsA, but not FK-506, induced gingival overgrowth associated with an increase of the salivary levels of the cytokines TGF-β1, EGF, and IL-6.

Treatment of experimental periodontal disease by a selective inhibitor of cyclooxygenase-2 with scaling and root planing (SRP)

Lumiracoxib is a selective inhibitor of cyclooxygenase-2 (COX-2) approved for the relief of symptoms of chronic inflammatory conditions. The aim of this study was to evaluate the effects of this specific inhibitor of COX-2 as adjunctive treatment on induced periodontitis in rats. Periodontal disease was induced at the first mandibular molar of 60 rats. After 7 days, the ligature was removed and all animals were submitted to scaling and root planing (SRP) along with local irrigation with saline solution and were divided into 2 groups: SRP (n = 30)-received subcutaneous injections of 1 mg/kg of body weight/day of saline solution for 3 days and; SRP + L (n = 30)-received subcutaneous injections of 1 mg/kg of body weight/day of Lumiracoxib for 3 days. Ten animals in each group were killed at 7, 15, and 30 days. The histological description was performed and the histometric values were statistically analyzed. In Group SRP + L, the histometric analysis (0.58 ± 0.08, 0.64 ± 0.06, and 0.56 ± 0.10 mm 2) showed less bone loss (p < 0.05) than Group SRP (1.52 ± 0.08, 1.55 ± 0.09, and 1.49 ± 0.24 mm 2) at 7, 15, and 30 days, respectively. Within the limits of this study it can be concluded that subcutaneous application of specific inhibitor of COX-2 was a beneficial adjunctive treatment for periodontal diseases induced in rats. © 2010 Springer Basel AG.