Jill D. Bashutski

Teriparatide and osseous regeneration in the oral cavity

BACKGROUND Intermittent administration of teriparatide, a drug composed of the first 34 amino acids of parathyroid hormone, has anabolic effects on bone. Although teriparatide has been evaluated for the treatment of osteoporosis and for the healing of fractures, clinical trials evaluating it for the treatment of osseous conditions of the oral cavity in humans are lacking. METHODS A total of 40 patients with severe, chronic periodontitis underwent periodontal surgery and received daily injections of teriparatide (20 μg) or placebo, along with oral calcium (1000 mg) and vitamin D (800 IU) supplementation, for 6 weeks. The patients were followed for 1 year. The primary outcome was a radiographic linear measurement of alveolar bone level. Secondary outcomes included clinical variables, bone turnover markers in serum and oral fluid, systemic bone mineral density, and quality of life. RESULTS Radiographic linear resolution of osseous defects was significantly greater after teriparatide therapy than after placebo beginning at 6 months, with a mean linear gain in bone at 1 year of 29% as compared with 3% (P<0.001). Clinical improvement was greater in patients taking teriparatide than in those taking placebo, with a reduction in periodontal probing depth of 33% versus 20% (2.42 mm vs. 1.32 mm) and a gain in clinical attachment level of 22% versus 7% (1.58 mm vs. 0.42 mm) in target lesions at 1 year (P = 0.02 for both comparisons). No serious adverse events were reported; however, the number of patients in the study was small. No significant differences were noted with respect to the other variables that were assessed. CONCLUSIONS Teriparatide, as compared with placebo, was associated with improved clinical outcomes, greater resolution of alveolar bone defects, and accelerated osseous wound healing in the oral cavity. Teriparatide may offer therapeutic potential for localized bone defects in the jaw. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00277706 .).

Periodontal and Endodontic Regeneration

Guided tissue regeneration (GTR) is effective in halting tissue and bone destruction and promoting new tissue and bone formation. Although the goal of complete and predictable regeneration still remains elusive, many techniques and materials have been developed that show good clinical and histologic outcomes. The most commonly used materials in GTR include bone replacement grafts from numerous sources, nonresorbable and bioabsorbable membranes, and recently growth hormones/cytokines and other host modulating factors. This article reviews the biologic rationale behind current techniques used for tissue/bone regeneration, reviews the most common materials and techniques, and attempts to explain the factors that influence the outcomes of these therapies.

The Impact of Vitamin D Status on Periodontal Surgery Outcomes

Vitamin D regulates calcium and immune function. While vitamin D deficiency has been associated with periodontitis, little information exists regarding its effect on wound healing and periodontal surgery outcomes. This longitudinal clinical trial assessed outcomes of periodontal surgery and teriparatide administration in vitamin-D-sufficient and -insufficient individuals. Forty individuals with severe chronic periodontitis received periodontal surgery, daily calcium and vitamin D supplements, and self-administered teriparatide or placebo for 6 wks to correspond with osseous healing time. Serum 25(OH)D was evaluated at baseline, 6 wks, and 6 mos post-surgery. Clinical and radiographic outcomes were evaluated over 1 yr. Placebo patients with baseline vitamin D deficiency [serum 25(OH)D, 16-19 ng/mL] had significantly less clinical attachment loss (CAL) gain (-0.43 mm vs. 0.92 mm, p < 0.01) and probing depth (PPD) reduction (0.43 mm vs. 1.83 mm, p < 0.01) than vitamin-D-sufficient individuals. Vitamin D levels had no significant impact on CAL and PPD improvements in teriparatide patients at 1 yr, but infrabony defect resolution was greater in teriparatide-treated vitamin-D-sufficient vs. -deficient individuals (2.05 mm vs. 0.87 mm, p = 0.03). Vitamin D deficiency at the time of periodontal surgery negatively affects treatment outcomes for up to 1 yr. Analysis of these data suggests that vitamin D status may be critical for post-surgical healing. (ClinicalTrials.gov number, CT00277706)

Implant Compression Necrosis : Current Understanding and Case Report

BACKGROUND Implants fail for a variety of reasons; it can be difficult to determine the exact cause of failure, especially if there are multiple contributing factors. Overcompression of the adjacent bone during implant placement is a potential contributing factor to implant failure that is not well documented in the literature. METHODS This case report reviews the concept of bone loss induced by overcompression and presents a case of implant failure with overcompression as a potential etiology. Histology, radiographs, and clinical data are presented that document the failure of four implants placed in the posterior mandible of a 48-year-old female patient. RESULTS After uneventful implant placement, one implant exfoliated 3 weeks postoperatively. The other three implants were removed because of severe bone loss up to 2 months later. Histology of the area revealed non-viable bony sequestra with bacterial colonization. CONCLUSIONS This case highlights unusual implant failures that likely occurred as a result of overcompression of the bone during placement. Areas involving dense bone seem to be at increased risk for compression necrosis.

Common implant esthetic complications.

Today, osseointegration of implants is readily attainable with high long-term survival rates. Consequently, clinicians are now focusing on improving implant esthetics and are starting to incorporate this parameter into their definition of implant success. However, studies measuring factors that affect implant esthetics and implant esthetic outcomes are lacking in the literature. A satisfactory esthetic outcome requires the clinician to be aware of the different factors affecting esthetics during the preplanning, surgical, and prosthetic phases of implant placement. This article addresses the etiologies of esthetic complications during each of these 3 phases and provides preventive and corrective treatment suggestions for these situations.

Effects of vitaxin®, a novel therapeutic in trial for metastatic bone tumors, on osteoclast functions in vitro

The integrin αvβ3 mediates cell–matrix interactions. Vitaxin®, a humanized monoclonal antibody that blocks human and rabbit αvβ3 integrins, is in clinical trials for metastatic melanoma and prostate cancer. αvβ3 is the predominant integrin on osteoclasts, the cells responsible for bone resorption in health and disease. Here, we report the first investigation of Vitaxins effects on osteoclast activity. Vitaxin (100–300 ng/ml) decreased total resorption by 50%, but did not alter resorptive activity per osteoclast. Vitaxin (300 ng/ml) decreased osteoclast numbers on plastic by 35% after 48 h. Similarly, attachment after 2 h was reduced by 30% when osteoclasts were incubated with Vitaxin (300 ng/ml) for 25 min prior to plating; however, the rate of fusion of osteoclast precursors in Vitaxin‐treated and control groups was equal. Using time‐lapse microscopy, we evaluated the effect of Vitaxin on osteoclast morphology and found a significant reduction in osteoclast planar area only when cells were pretreated with macrophage colony stimulating factor (M‐CSF). Extracellular Ca2+ and M‐CSF have opposite effects on αvβ3 conformation. Elevation of extracellular Ca2+ eliminated the inhibitory effect of Vitaxin on osteoclast attachment. In contrast, the effect of Vitaxin was enhanced in cells pretreated with M‐CSF. This action of M‐CSF was suppressed by the phosphatidylinositol 3‐kinase (PI3‐kinase) inhibitor wortmannin, suggesting that M‐CSF increases Vitaxins inhibitory effect by inside‐out activation of αvβ3. In conclusion, Vitaxin decreases resorption by impairing osteoclast attachment, without affecting osteoclast formation and multinucleation. Our data also show that Vitaxins inhibitory effects on osteoclasts can be modulated by factors known to alter the conformation of αvβ3. J. Cell. Biochem. 102: 341–352, 2007.

The Effect of Flapless Surgery on Implant Survival and Marginal Bone Level: A Systematic Review and Meta-Analysis

BACKGROUND The clinical outcomes of implants placed using the flapless approach have not yet been systematically investigated. Hence, the present systematic review and meta-analysis aims to study the effect of the flapless technique on implant survival rates (SRs) and marginal bone levels (MBLs) compared with the conventional flap approach. METHODS An electronic search of five databases (from 1990 to March 2013), including PubMed, Ovid (MEDLINE), EMBASE, Web of Science, and Cochrane Central, and a hand search of peer-reviewed journals for relevant articles were performed. Human clinical trials with data on comparison of SR and changes in MBL between the flapless and conventional flap procedures, with at least five implants in each study group and a follow-up period of at least 6 months, were included. RESULTS Twelve studies, including seven randomized controlled trials (RCTs), one cohort study, one pilot study, and three retrospective case-controlled trials (CCTs), were included. The SR of each study was recorded, weighted mean difference (WMD) and confidence interval (CI) were calculated, and meta-analyses were performed for changes in MBL. The average SR is 97.0% (range, 90% to 100%) for the flapless procedure and 98.6% (range, 91.67% to 100%) for the flap procedure. Meta-analysis for the comparison of SR among selected studies presented a similar outcome (risk ratio = 0.99, 95% CI = 0.97 to 1.01, P = 0.30) for both interventions. Mean differences of MBL were retrieved from five RCTs and two retrospective CCTs and subsequently pooled into meta-analyses; however, none of the comparisons showed statistical significance. For RCTs, the WMD was 0.07, with a 95% CI of -0.05 to 0.20 (P = 0.26). For retrospective CCTs, the WMD was 0.23, with a 95% CI of -0.58 to 1.05 (P = 0.58). For the combined analysis, the WMD was 0.03, with a 95% CI of -0.11 to 0.18 (P = 0.67). The comparison of SR presented a low to moderate heterogeneity, but MBL presented a considerable heterogeneity among studies. CONCLUSION This systematic review revealed that the SRs and radiographic marginal bone loss of flapless intervention were comparable with the flap surgery approach.

Retrograde Peri-Implantitis: A Case Report Introducing an Approach to Its Management

BACKGROUND Although several potential etiologic factors associated with retrograde peri-implantitis (RPI) and potential treatment options have been discussed in the literature, the etiology has not been fully investigated and the definitive management methods remain undefined. We propose a decision-making protocol for the treatment of RPI and provide new insight into the etiology of this process based on the findings from two clinical cases. METHODS The medical and dental histories of two patients who developed RPI were thoroughly reviewed. Both patients were treated according to the treatment guidelines proposed in this manuscript. Fluid from the lesions was collected to examine the presence of 11 bacterial species by molecular-based microbial testing. Biopsies were also obtained for histopathologic examination. RESULTS Patient 1, previously diagnosed with human immunodeficiency virus infection, developed RPI 3 months after implant placement. Histopathologic examination revealed a predominantly fibrous connective tissue response with minimal inflammatory infiltrate and bone formation. Patient 2 presented histopathologically with an intense acute inflammatory response. Eikenella corrodens was detected by microbial testing. Three months after surgical intervention, both cases healed uneventfully, and the radiodensity in the lesions significantly increased. The two implants are now functional and free of further complications. CONCLUSIONS The possible role of bacterial infection from an adjacent tooth may be a potential etiologic factor in the development of RPI. In addition, HIV infection may be associated with RPI and deserves further investigation. A decision-making flowchart was proposed after critically evaluating the currently available relevant literature. Both cases presented in this manuscript were successfully treated by following this protocol.

Effect of Flapless Surgery on Single-Tooth Implants in the Esthetic Zone: A Randomized Clinical Trial

BACKGROUND Implant therapy is a highly predictable treatment option; however, insufficient data exist to show whether flapless implant surgery provides better esthetic outcomes and less bone loss than implant surgery with a flap approach. METHODS In this randomized, controlled study comparing the flapless and traditional flap protocol for implant placement, 24 patients received a single implant in the anterior maxillary region. A cone beam computed tomography-aided surgical guide was used for implant placement surgery for both groups. Implants were restored using a one-piece, screw-retained ceramic crown at 3 months. Radiographic and clinical measurements were assessed at baseline (implant placement) and at 3 (crown placement), 6, 9, and 15 months. Clinical parameters evaluated were plaque index, gingival index, papillary index (PPI) (0 = no papilla, 1 = less than half, 2 = more than half but not complete, 3 = complete fill, and 4 = overfill), marginal tissue levels, biotype, width of keratinized tissue, and soft tissue thickness. RESULTS Implant success rate was 92% in both groups. Mean PPI values for the flap control group and flapless test group were 2.38 ± 0.51 versus 2.31 ± 0.48 at crown placement (P = 0.68) and 2.52 ± 0.52 versus 2.64 ± 0.54 at 15 months (P = 0.42), respectively. PPI increased over time in both groups, although the flapless group had a significantly larger change in PPI from crown placement to 6 and 9 months (P <0.01). Crestal bone levels in the flap group were more apical in relation to the implant platform than those in the flapless group for the duration of the study. No differences among groups were noted for all other measurements. CONCLUSIONS Both flapless and flap implant placement protocols resulted in high success rates. A flapless protocol may provide a better short-term esthetic result, although there appears to be no long-term advantage.

Early implant bone loss: Preventable or inevitable?

Early implant bone loss (EIBL) is defined as the periimplant crestal bone loss occurring from fixture installation to 1 year after loading. This phenomenon has been suggested to be associated with biologic and biomechanical factors. Minimizing EIBL at every treatment step is preferable because this may improve implant health, aesthetics, and overall success. This review presents the host-related factors, implant design characteristics, and the surgical and restorative protocol modifiers that should be evaluated during therapy. Host-related factors may involve the healing capacity, periodontal status, and occlusal function. Implant design features to be considered include the control of biologic width, microgap, and crestal stress distribution. Finally, surgical and restorative factors to be considered are implant site development, minimally invasive surgical approach, implant positioning, and the restorative design and occlusal scheme. Rationale and strategies to control the modifiable factors are also proposed.