Efficacy of locally delivered statins as an adjunct to scaling and root planning in the treatment of periodontitis: a systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review is to assess the efficacy of locally delivered statins used in adjunct to scaling and root planing (SRP), compared with SRP alone. MATERIALS AND METHODS: An electronic and hand search was carried out up to April 2020. Only randomized controlled trials (RCTs) were included. Clinical attachment level gain (CALgain) and probing depth reduction (PDred), modified sulcular bleeding index reduction (mSBIred), and intrabony defect reduction (IBDred) were the investigated outcomes. Meta-analysis was performed, and the power of the meta-analytic findings was determined by trial sequential analysis (TSA). Studies were also sub-grouped based on the type of statin used. Statistical heterogeneity and publication bias were assessed. RESULTS: Twenty RCTs were included (1212 patients, 1289 defects). An overall statistically significant effect size in favor of statins for CALgain and PDred was found. As opposed to atorvastatin and rosuvastatin, simvastatin did not reach statistical significance for these outcomes, as shown by the sub-group analysis. CONCLUSIONS: Within the limits of the available studies, the local administration of statins (in particular, atorvastatin and rosuvastatin) in adjunct to SRP may result in additional significant improvement in terms of CALgain and PDred compared with SRP alone. The high heterogeneity of data and the high risk of bias found, however, impose caution. No approved preparations, moreover, exist, and further well-designed RCTs from independent research centers are needed to confirm the beneficial effects of the different statins and their mutual differences in the non-surgical periodontal treatment.

A prospective, randomized trial for the prevention of mucositis in patients undergoing hematopoietic stem cell transplantation.

Oral mucositis is a complication common to many cancer therapies and produces considerable pain and morbidity. The present study reports a double-blind, prospective, randomized clinical trial testing the efficacy of a calcium phosphate mouth rinse (Caphosol) with fluoride treatments vs a standard regimen of fluoride rinsing and placebo tray treatments in 95 patients undergoing hematopoietic stem cell transplantation (HSCT). The days and severity of mucositis were prospectively evaluated. There were statistically significant decreases in days of mucositis (3.72 vs 7.22 P=0.001), duration of pain (2.86 vs 7.67, P=0.0001), dose of morphine (34.54 mg vs 122.78 mg), days of morphine (1.26 vs 4.02, P=0.0001) and days to the onset of engraftment ANC (absolute neurotrophil count)>200 mm(3) (11.12 vs 12.56) in the Caphosol and fluoride treatment group vs fluoride-rinse group, respectively. Caphosol, a neutral, supersaturated, Ca(2+)/PO(4)(3-) mouth rinse, used in combination with topical fluoride treatments, is superior to fluoride rinse alone in reducing the frequency, intensity and duration of oral mucositis in patients undergoing HSCT.

The effect of interleukin-11 on the progression of ligature-induced periodontal disease in the beagle dog.

BACKGROUND: The rate of progression of periodontal disease is dependent on the complex regulatory interactions between bacteria and the immune modulators of the host response. The purpose of this investigation was to determine if recombinant human interleukin-11 (rhIL-11), known to downregulate several inflammatory modulators, has the ability in subcutaneous administration to reduce the rate and/or extent of periodontal attachment loss and radiographic bone loss in a ligature-induced periodontal disease beagle dog model. METHODS: Twenty 18-month-old female beagle dogs were brought to optimal periodontal health over a 2-week period. Periodontal disease was induced by placing 2.0 silk ligatures around the mandibular first molar and premolar teeth. The dogs were divided into 3 treatment groups and one control group. The 3 treatment groups received subcutaneous injections of either 15, 30, or 80 microg/kg of rhIL-11 in saline buffer twice a week. The placebo group received buffer only subcutaneously twice a week. The gingival health of each animal was measured by recording the presence or absence of gingival inflammation, plaque, and bleeding upon probing. Attachment levels and bone height were also measured. Treatment administration and clinical and radiographic evaluations were performed in a masked fashion. RESULTS: At week 8, the placebo group had 3.89 mm of attachment loss and 73.8% radiographic bone remaining. The 15 microg/kg group had 1.99 mm attachment loss and 89.5% bone remaining; the 30 microg/kg group had 0.84 mm attachment loss and 92.5% bone remaining; and the 80 microg/kg group had 1.05 mm attachment loss and 85.5% bone remaining. All 3 treatment groups lost significantly less attachment and retained significantly more bone than did the placebo group. CONCLUSIONS: The study indicates that subcutaneous injections of rhIL-11 were able to slow the progression of attachment and radiographic alveolar bone loss in a ligature-induced beagle dog model.

Long-term evaluation of osseointegrated implants in regenerated and nonregenerated bone.

This investigation evaluated the predictability of dental implants subjected to bone regeneration procedures at the time of insertion. Fifty-two test implants were inserted into sites with periimplant bone defects. A calcium carbonate allograft material with or without a fibrin-fibronectin sealing system was used to fill the defects. Sixty control implants were inserted into an adequate volume of nonaugmented bone. Each of the 29 study patients received at least one test implant and one control implant. At the second-stage surgery, fill of the bone defect was assessed as complete or incomplete. The cumulative success rate was 91.7% (mean follow-up 55 mo) for the test implants and 93.2% (mean follow-up 59 mo) for the control implants. Within the test group, implants with complete bone fill achieved 97.6% success versus 59.1% success for implants with incomplete bone fill. These preliminary results suggest that implants placed with simultaneous bone regeneration procedures achieve long-term predictability that is comparable to that of implants placed in an adequate volume of bone, provided that complete bone fill of the periimplant defect is achieved. Long-term studies with other augmentation materials are needed to fully validate these findings.

Enantiospecific inhibition of ligature-induced periodontitis in beagles with topical (S)-ketoprofen.

Systemic and topical administration of non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce periodontal disease progression in both animal models and human subjects. Our present research focuses on single enantiomers of these agents to examine whether enantiospecific therapy will be efficacious in slowing periodontitis. The purpose of this study was to evaluate the inhibitory effects of (S)-ketoprofen on experimentally induced alveolar bone loss in beagle dogs. 16, 18-month-old, female beagles were brought to optimal periodontal health over a 2-week pretreatment period. Experimental periodontitis was then induced by placing silk ligatures around premolar and molar teeth and by instituting a soft, plaque-promoting diet. At baseline, animals were randomized to 1 of 4 groups, consisting of 2x daily administration of (1) placebo dentifrice, (2) 0.3% (S)-ketoprofen dentifrice, (3) 3.0% (S)-ketoprofen dentifrice, or (4) 10.0 mg (S)-ketoprofen capsules (p.o.) over a 60 day treatment period. Standardized, periapical radiographs exposed at days 1 and 60 were analyzed by computer-assisted digital radiography in order to assess the rate of alveolar bone loss. Secondary outcomes included technetium 99m-tin-diphosphonate (99mTc-Sn-MDP) uptake and the gingival index. At baseline, no differences were observed among the groups for linear bone height or 99mTc-Sn-MDP uptake ratios. From days 1 to 60, cohorts differed significantly in terms of bone loss rates (p < 0.001). In particular, beagles treated with systemic or topical (S)-ketoprofen (0.3% or 3.0% dentifrices) exhibited significantly lower mean rates of bone loss compared to placebo treated beagles (p < 0.05). Group differences in mean radiopharmaceutical uptake ratio changes approached significance (ANOVA, p = 0.07), where animals treated with topical 0.3% (S)-ketoprofen demonstrated a reduction and other groups demonstrated elevations over the 60-day dosing period. Treatment cohorts did differ significantly with respect to changes in mean gingival indices (p < 0.05). Animals treated with 0.3% or 3.0% (S)-ketoprofen dentifrice exhibited significantly reduced elevations in gingival index scores as compared to placebo treated animals. These data provide evidence that enantiospecific therapy with (S)-ketoprofen, topically or systemically delivered, may alter the progression of periodontal disease in the beagle dog model.

The use of replicate resin models in the treatment of maxillary sinus augmentation patients.

The elevation of the floor of the maxillary sinus is becoming a routine surgical procedure to develop the site for dental implants. This delicate procedure is best performed with diagnostics of the highest magnitude. To this point, computer tomographic scans provide valuable information, especially when defining the location and extension of septae transversing the sinus. Additional useful information is provided by a replicate resin model that is constructed from a magneto-optical disk compatible with a personal computer. The image data is then converted to a DOS format. Bone structures of interest are thresholded in each slice based on single-pixel gray levels. Object profiles with linear interpolation and their elaboration generate the three-dimensional surface of the object. Finally, the physical resin model is fabricated.

Supracrestal bone regeneration around dental implants using a calcium carbonate and a fibrin-fibronectin sealing system: clinical and histologic evidence.

This study evaluated a new surgical technique for the treatment of an alveolar ridge deficiency in 11 patients. Twenty-two implants were placed, 15 of which presented with a combination of supracrestal and dehiscence kinds of defects, and seven presented only supracrestal bone loss. Surgical procedures were performed utilizing a combination of the resorbable space-making material calcium carbonate stabilized with a fibrin-fibronectin sealing system and the immediate placement of titanium dental implants. After implant placement, the mean height for supracrestal and dehiscence defects measured 2.57 +/- 1.41 mm and 2.47 +/- 1.54 mm, respectively. The defects were filled with calcium carbonate and a fibrin-fibronectin sealing system, and the flaps were sutured, avoiding any compression of the treated area. Healing was uneventful in all instances. At second-stage surgery at 6 months, a hard bone-like tissue was detectable at the defect sites. Histologic examination of four defects confirmed the presence of newly formed bone and revealed residual particles of calcium carbonate. There was a mean gain of 2.05 +/- 1.47 mm in the supracrestal defects and of 2.23 +/- 1.62 mm in the dehiscences. The results indicated that calcium carbonate, combined with a fibrin-fibronectin sealing system, is a viable alternative in the treatment of supracrestal and dehiscence bony defects.

Polypeptide growth factors for periodontal regeneration.

The regeneration of periodontal attachment apparatus is particularly difficult to achieve, primarily because of the presence of many different kinds of tissue that must be restored to produce a functional unit. Traditional methods aimed at regenerating the periodontium have limited indications, and their results are not predictable. Recently, investigators have begun to understand the cellular processes necessary for repair and regeneration of periodontal tissues. Proteins called growth factors have been identified that coordinate these cellular events. The growth factors that may contribute to periodontal regeneration include platelet-derived growth factor, insulin-like growth factor, transforming growth factor-beta, and bone morphogenetic proteins. In vitro studies have demonstrated the positive effects of these factors on a number of cell types essential for periodontal regeneration. For instance, it has been shown that platelet-derived and insulin-like growth factors promote proliferation of osteoblasts an periodontal ligament cell-derived fibroblasts. Animal models have also been used to verify that growth factors can enhance regeneration in vivo following periodontal disease and as an adjunct to implant placement. In the future, human clinical trials will be required to identify the ideal growth factors, their proper doses, and the most suitable carrier system for them.

Allosteric inhibition of the water-soluble C-terminal fragment of Sendai virus neuraminidase.

Trypsin solubilized hemagglutinin-neuraminidase of Sendai virus (cHN) displays michaelian kinetics, with native fetuin as substrate, at 37 degrees C. Vmax and Km values are only marginally altered, as compared to intact viral neuraminidase. At lower temperatures, cHN follows non-michaelian kinetics, with marked substrate inhibition at 4 degrees C. With denaturated fetuin, michaelian kinetics are observed in all conditions, while asialo fetuin was an uncompetitive inhibitor of cHN, with native fetuin or sialyl lactose as substrates. These results can be explained assuming that the protein moiety of fetuin acts as an allosteric inhibitor of cHN.