Brian L. Mealey

Diabetes mellitus and inflammatory periodontal diseases

PURPOSE OF REVIEW Periodontal diseases are inflammatory conditions that were once thought to have manifestations localized to the oral cavity alone, and were therefore considered the concern of only dentists and other oral health professionals. Emerging evidence has changed this view and now suggests that periodontal diseases may play a role in numerous conditions that impact systemic well being, including diabetes mellitus. This review examines the relationships that exist between periodontal diseases and diabetes mellitus, with a focus on potential common pathophysiologic pathways including those associated with inflammation, altered host responses, and insulin resistance. RECENT FINDINGS Periodontal inflammation is associated with an elevated systemic inflammatory state and an increased risk of major cardiovascular events such as myocardial infarction and stroke, adverse pregnancy outcomes such as preeclampsia, low birth weight and preterm birth, and altered glycemic control in people with diabetes. Intervention trials suggest that periodontal therapy, which decreases the intraoral bacterial bioburden and reduces periodontal inflammation, can have a significant impact on systemic inflammatory status. Evidence suggests that periodontal therapy is associated with improved glycemic control in many patients with both diabetes and periodontal diseases. SUMMARY Recognition of the bilateral relationships between oral and systemic health will challenge physicians and dentists to work together closely in the future when managing patients with diabetes and periodontal disease.Purpose of reviewPeriodontal diseases are inflammatory conditions that were once thought to have manifestations localized to the oral cavity alone, and were therefore considered the concern of only dentists and other oral health professionals. Emerging evidence has changed this view and now suggests that periodontal diseases may play a role in numerous conditions that impact systemic well being, including diabetes mellitus. This review examines the relationships that exist between periodontal diseases and diabetes mellitus, with a focus on potential common pathophysiologic pathways including those associated with inflammation, altered host responses, and insulin resistance. Recent findingsPeriodontal inflammation is associated with an elevated systemic inflammatory state and an increased risk of major cardiovascular events such as myocardial infarction and stroke, adverse pregnancy outcomes such as preeclampsia, low birth weight and preterm birth, and altered glycemic control in people with diabetes. Intervention trials suggest that periodontal therapy, which decreases the intraoral bacterial bioburden and reduces periodontal inflammation, can have a significant impact on systemic inflammatory status. Evidence suggests that periodontal therapy is associated with improved glycemic control in many patients with both diabetes and periodontal diseases. SummaryRecognition of the bilateral relationships between oral and systemic health will challenge physicians and dentists to work together closely in the future when managing patients with diabetes and periodontal disease.

American Academy of Periodontology Task Force report on the update to the 1999 classification of periodontal diseases and conditions

In 2014, the American Academy of Periodontology Board of Trustees charged a Task Force to develop a clinical interpretation of the 1999 Classification of Periodontal Diseases and Conditions to address concerns expressed by the education community, the American Board of Periodontology, and the practicing community that the current Classification presents challenges for the education of dental students and implementation in clinical practice. The Academy announced that an update to the 1999 Classification would commence in 2017. The present focused update addresses three specific areas of concern with the current classification: attachment level, chronic versus aggressive periodontitis, and localized versus generalized periodontitis.

Histologic comparison of healing after tooth extraction with ridge preservation using mineralized versus demineralized freeze-dried bone allograft.

BACKGROUND Allografts, such as demineralized freeze-dried bone allograft (DFDBA) and mineralized freeze-dried bone allograft (FDBA) are commonly used by clinicians for ridge preservation procedures. The primary objective of this study is to histologically evaluate and compare the healing of non-molar extraction sockets grafted with DFDBA versus FDBA for ridge preservation. The secondary aim of this study is to compare dimensional changes in ridge height and width after grafting with these two materials. MATERIALS Forty patients were randomly divided into two groups of 20. Extraction sockets were filled with either FDBA or DFDBA. To minimize variables associated with the organ donor and with tissue processing, all of the graft material was procured from a single donor; the only difference in the two materials was the percentage mineralization of the final bone graft. A 2-mm-diameter core biopsy was taken from each grafted site ≈19 weeks after grafting. Histomorphometric analysis was performed to determine percentage of vital bone, residual graft particles, and connective tissue (CT)/other non-bone components. RESULTS There were no significant differences when comparing changes in alveolar ridge dimensions of the two groups. There was no significant difference in percentage CT/other between groups. DFDBA had a significantly greater percentage of vital bone at 38.42% versus FDBA at 24.63%. The DFDBA group also had a significantly lower mean percentage of residual graft particles at 8.88% compared to FDBA at 25.42%. CONCLUSION This study provides the first histologic and clinical evidence directly comparing ridge preservation with DFDBA versus FDBA in humans and demonstrates significantly greater new bone formation with DFDBA.

Response of chronic and aggressive periodontitis to treatment.

Patients with aggressive periodontitis can be both rewarding and frustrating to treat in clinical practice. Interindividual variation in response to therapy can be widespread, and we do not clearly understand the reasons for this variable response. It is possible that new research into the resolution of inflammation may reveal basic differences between patients with chronic periodontitis and those with aggressive disease. In addition, future research involving modulation of host inflammatory responses may clarify the reasons for the differences in clinical outcomes between patients. We think it likely that this research could result in further alterations to the classification of periodontal diseases, as with more knowledge of the mechanisms of disease it is possible that patients currently classified as having aggressive periodontitis may be found not to represent a single diagnostic entity. Better understanding of the true nature of patients currently identified as having aggressive periodontitis may therefore lead to more effective treatment approaches.

Histologic analysis of healing after tooth extraction with ridge preservation using mineralized human bone allograft

BACKGROUND Ridge preservation was developed as a therapy to prevent severe bone resorption after tooth extraction. The purpose of this study is to determine if there is any difference in the amount of new bone formation ≈3 months after extraction and ridge preservation compared to that after ≈6 months. METHODS Minimally traumatic extraction with ridge preservation using mineralized human bone allograft was performed at 38 single-rooted tooth sites in 33 subjects. Sixteen sites healed for an average of 14 weeks (early healing), whereas 22 sites were allowed to heal for an average of 27 weeks (delayed healing) before harvesting bone core samples. Histomorphometric analysis was performed to determine the percent of new bone formation, residual graft particles, and connective tissue/non-mineralized structures for each site. RESULTS All specimens showed evidence of new bone formation, with most of the residual graft particles surrounded intimately by woven bone. No statistically significant differences in the amount of newly formed bone or residual graft particles were found between the two groups. Overall, the early healing group demonstrated a mean of 45.8% new bone, 14.6% residual graft material, and 39.6% connective tissue/non-mineralized tissue. The delayed healing group showed mean values of 45%, 13.5%, and 41.3%, respectively. CONCLUSION The results of this study suggest that waiting ≈6 months after tooth extraction and ridge preservation using mineralized bone allograft does not provide a greater amount of new bone formation or less residual bone particles compared to that after only ≈3 months.

Evaluation of healing following tooth extraction with ridge preservation using cortical versus cancellous freeze-dried bone allograft.

BACKGROUND The objective of this study is to compare histologic and clinical healing following tooth extraction and ridge preservation with either cortical or cancellous freeze-dried bone allograft (FDBA) in non-molar extraction sockets. METHODS Forty patients requiring implant placement were enrolled, with 20 patients randomly assigned to each group (cortical versus cancellous FDBA). All of the allograft materials were obtained from the same donor to control for variability between donors and processing. Patients returned after 17 to 21 weeks (average: 18.2 weeks), and a 2-mm-diameter core biopsy was obtained before implant placement. Histomorphometric analysis was performed to determine percentage of new bone formation, residual graft material, and non-mineralized connective tissue (CT)/other material. Clinical measurements of ridge dimensions were taken at the time of tooth extraction and again at implant placement. RESULTS There was no significant difference in new bone formation between the cortical and cancellous FDBA groups (P = 0.857). A significantly greater percentage of residual graft material was detected in the cortical FDBA group compared with the cancellous FDBA group (P = 0.019). A significantly greater percentage of non-mineralized CT/other material was found in the cancellous FDBA group compared with the cortical FDBA group (P = 0.040). The only significant clinical difference between groups was a greater loss of lingual ridge height in the cancellous group. CONCLUSIONS This is the first reported study to compare the histologic changes following tooth extraction with ridge preservation in humans using cortical versus cancellous FDBA. There were no differences in the percentage of new bone formation between the groups.

Histologic Comparison of Healing After Ridge Preservation Using Human Demineralized Bone Matrix Putty With One Versus Two Different-Sized Bone Particles

BACKGROUND Ridge preservation can minimize the loss of alveolar bone subsequent to tooth extraction in preparation for implant therapy. The purpose of this study is to histologically and clinically compare human demineralized bone matrix (DBM) putty with one size of bone particles (SPS) to human DBM putty with two different sizes of bone particles (multiple particle sizes [MPS]) in ridge preservation after molar extractions. METHODS Molar tooth extraction and ridge preservation were performed in 20 participants for each treatment group. Approximately 20 weeks after grafting, core biopsies were obtained during implant placement and analyzed under light microscopy. Specimens were analyzed for the percentage area of vital bone, residual graft particles, and non-mineralized structures (connective tissue/other non-mineralized tissue [CT]). Changes in alveolar ridge dimensions were also determined. RESULTS Sixteen participants in the SPS group and 14 in the MPS group completed the study. The SPS group had a mean of 49% vital bone, 8% residual graft, and 43% CT. The MPS group had 53%, 5%, and 42%, respectively. Patients in both groups lost a mean of <1 mm alveolar height on the buccal and lingual aspects and <1.5 mm of total ridge width. There were no statistically significant differences between the two groups for any clinical or histologic parameters. CONCLUSION The results of this study suggest that addition of larger bone particles to DBM putty does not offer additional benefit in the preservation of alveolar bone after the extraction of molar teeth.

Buccal Bone Formation After Flapless Extraction: A Randomized, Controlled Clinical Trial Comparing Recombinant Human Bone Morphogenetic Protein 2/Absorbable Collagen Carrier and Collagen Sponge Alone

BACKGROUND Flapless extraction of teeth allows for undisturbed preservation of the nearby periosteum and a source of osteoprogenitor cells. Recombinant human bone morphogenetic protein 2 (rhBMP-2) has been used for different bone augmentation purposes with great osteoinductive capacity. The aim of this study is to compare the bone regenerative ability of rhBMP-2 on an absorbable collagen sponge (ACS) carrier to a collagen sponge (CS) alone in extraction sites with ≥50% buccal dehiscence. METHODS Thirty-nine patients requiring extraction of a hopeless tooth with ≥50% buccal dehiscence were enrolled. After flapless extraction and randomization, either rhBMP-2/ACS carrier or CS alone was placed in the extraction site. After extraction, a baseline cone beam computed tomography (CBCT) scan was obtained of the site, and a similar scan was obtained 5 months postoperatively. Medical imaging and viewing software were used to compare the baseline and 5-month postoperative images of the study site and assess ridge width measurements, vertical height changes, and buccal plate regeneration. RESULTS Radiographically, CBCT analysis showed that with ≥50% of buccal bone destruction, rhBMP-2/ACS was able to regenerate a portion of the lost buccal plate, maintain theoretical ridge dimensions, and allow for implant placement 5 months after extraction. The test group performed significantly (P <0.05) better in regard to clinical buccal plate regeneration (4.75 versus 1.85 mm), clinical ridge width at 5 months (6.0 versus 4.62 mm), and radiographic ridge width at 3 mm from the alveolar crest (6.17 versus 4.48 mm) after molar exclusion. There was also significantly (P <0.05) less remaining buccal dehiscence, both clinically (6.81 versus 10.0 mm) and radiographically (3.42 versus 5.16 mm), at 5 months in the test group. Significantly (P <0.05) more implants were placed in the test group without the need for additional augmentation. The mean loss in vertical ridge height (lingual/palatal) was less in the test sites but was not significantly (P = 0.514) different between the test and control groups (0.39 versus 0.64 mm). CONCLUSIONS rhBMP-2/ACS compared to CS alone used in flapless extraction sites with a buccal dehiscence is able to regenerate lost buccal plate, maintain theoretical ridge dimensions, and allow for implant placement 5 months later.

Molecular heterogeneity of PAF in normal human mixed saliva: quantitative mass spectral analysis after direct derivatization of PAF with pentafluorobenzoic anhydride

Platelet-activating factor (PAF), a family of phospholipid autacoids with potent pro-inflammatory activities, is present in saliva. The current study has quantitated various species of PAF isolated from normal human mixed saliva. Choline-containing, sn-2 acetylated phospholipids with sn-1 ether- or ester-linked fatty alcohol/acid moieties (alkyl-PAF or acyl-PAF, respectively) were evaluated after direct derivatization with pentafluorobenzoic (PFB) anhydride. Individual species of PFB-derivatized PAF were separated by gas chromatography prior to mass spectral analysis; quantitative estimates of six different species of PAF in saliva were made by comparison to corresponding authentic, synthetic PAF standards. In each saliva sample, all six species of PAF were readily detected by this facile procedure. The predominant PAF was 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine or 16:0-alkyl-PAF (0.75 +/- 0.09 pmol/ml saliva; mean +/- S.E.; n = 5) which represented only 30.4 +/- 1.5% of the total PAF. Substantial amounts of 18:1- and 18:0-alkyl-PAF and 16:0-acyl-PAF were also identified (0.52 +/- 0.07, 0.35 +/- 0.06, and 0.35 +/- 0.02 pmol/ml saliva, respectively). In summary, mass spectrometric analysis of PAF after direct derivatization with PFB anhydride has revealed that at least six different species of PAF are present in normal human mixed saliva. This structural diversity may represent an important aspect of homeostasis in the healthy oral cavity.

Histologic Comparison of Healing Following Tooth Extraction With Ridge Preservation Using Two Different Xenograft Protocols

BACKGROUND The objectives of this study are to compare differences in histologic and clinical healing following tooth extraction and ridge preservation using two different xenograft treatment protocols. METHODS Forty-four patients with a non-molar tooth that required extraction and planned implant placement were randomly allocated into two ridge preservation protocol groups. Protocol 1 used a xenograft material consisting of 90% anorganic bovine bone in combination with 10% porcine collagen fibers combined with a resorbable bilayer membrane composed of non-cross-linked porcine types I and III collagen. Protocol 2 used a xenograft sponge composed of 70% cross-linked type I bovine collagen coated with a layer of non-sintered hydroxyapatite mineral on its surface combined with a resorbable membrane composed of type I porcine collagen cross-linked by natural ribose glycation. Following 21 weeks of healing, clinical measurements were repeated, and a core biopsy was obtained and prepared for histologic evaluation of percentages of vital bone, residual graft, and connective tissue/other (CT/other). RESULTS Similar percentages of CT/other were detected between protocols, with no significant difference between groups (P = 0.763). A significantly greater percentage of vital bone was detected in specimens in protocol 2 (P <0.001). Protocol 1 presented with a mean of 32.83% ± 14.72% vital bone, 13.44% ± 11.57% residual graft material, and 53.73% ± 6.76% CT/other. Protocol 2 presented with a mean of 47.03% ± 9.09% vital bone, no detectable residual graft material, and 52.97% ± 9.09% CT/other. Clinically, no significant differences in dimensional changes were evident between ridge preservation protocols. CONCLUSION To the best of our knowledge, this study represents the first randomized controlled trial to evaluate clinical and histologic differences seen when using these two xenograft protocols for ridge preservation.