Mohanad Al-Sabbagh

Bone Remodeling Associated Salivary Biomarker MIP-1α Distinguishes Periodontal Disease from Health

BACKGROUND AND OBJECTIVE The field of salivary diagnostics lacks an accepted and validated biomarker of alveolar bone remodeling. To address this, we examined levels of salivary biomolecules specifically associated with biological aspects of bone remodeling in subjects with chronic periodontitis in a case-control study. MATERIAL AND METHODS Levels of macrophage inflammatory protein-1α (MIP-1α), osteoprotegerin, C-telopeptide pyridinoline cross-links of type I collagen and β-C-terminal type I collagen telopeptide in unstimulated whole saliva of 80 subjects (40 subjects with moderate to severe chronic periodontitis and 40 sex- and age-matched healthy control subjects) were measured using enzyme immunosorbent assays. Saliva was collected before clinical examination, which included probing depth, clinical attachment loss and bleeding on probing. RESULTS The mean level of MIP-1α in subjects with periodontitis was 18-fold higher than in healthy subjects (p < 0.0001). Clinical periodontal indices correlated significantly with MIP-1α levels (p < 0.0001). Of the biomolecules examined, MIP-1α demonstrated the greatest ability to discriminate between periodontal disease and health as determined by the area under the curve (0.94) and classification and regression tree analysis (sensitivity 94% and specificity 92.7%). Osteoprotegerin levels were elevated 1.6-fold (p = 0.055), whereas C-telopeptide pyridinoline cross-links of type I collagen and β-C-terminal type I collagen telopeptide levels were below the level of detection in the majority of subjects. CONCLUSION These findings suggest that the chemokine MIP-1α may aid in identifying periodontitis. Future longitudinal studies are warranted to determine whether this biomarker can help in ascertaining the progression of bone loss in subjects with periodontal disease.

Within-Subject Variability in Repeated Measures of Salivary Analytes in Healthy Adults

BACKGROUND Saliva contains a large number of biomolecules, some of which have putative diagnostic usefulness. A potential problem with the use of biomolecules in diagnosis is day-to-day fluctuation due to within-subject variability. This study evaluated the intraindividual variability of six salivary analytes in healthy adults and determined their normal range. METHODS Unstimulated whole saliva (5 ml) was collected every 2 to 3 days on six occasions from 30 subjects in good oral and systemic health. Four of the samples were collected in the clinic, and two were collected by the subject at home. The concentration ranges of interleukin (IL)-1beta, IL-6, matrix metalloproteinase-8, prostaglandin E(2), tumor necrosis factor-alpha, interferon-alpha, and albumin were examined. Descriptive statistics were computed, and a one-way random-effects model was used to quantify within- and between-subject components of variability. Intraclass correlation coefficients (ICCs) were calculated for each subject/analyte combination. RESULTS Within-subject coefficients of variation for these analytes ranged from 67.6% to 172.1% for the in-clinic samples and from 111.9% to 201.0% for the at-home samples. The ICC for the various analytes ranged from 41% to 61% for the in-clinic samples. The at-home samples exhibited significantly more variability than did those obtained in the clinic under supervision. CONCLUSIONS There was marked within-subject variation in the salivary concentrations of these analytes. With increased interest in salivary diagnostics, the within-subject variability, normal range, and threshold levels for abnormal levels of individual salivary analytes need to be determined if these diagnostics tests are to have clinical usefulness.

Salivary Biomarkers Associated With Gingivitis and Response to Therapy

BACKGROUND Salivary biomarkers are potentially important for determining the presence, risk, and progression of periodontal disease. However, clinical translation of biomarker technology from lab to chairside requires studies that identify biomarkers associated with the transitional phase between health and periodontal disease (i.e., gingivitis). METHODS Eighty participants (40 with gingivitis, 40 healthy) provided saliva at baseline and 7 to 30 days later. An additional sample was collected from gingivitis participants 10 to 30 days after dental prophylaxis. Clinical parameters of gingival disease were recorded at baseline and the final visit. Salivary concentrations of interleukin (IL)-1β, IL-6, matrix metalloproteinase (MMP)-8, macrophage inflammatory protein (MIP)-1α, and prostaglandin E2 (PGE2) were measured. RESULTS Clinical features of health and gingivitis were stable at both baseline visits. Participants with gingivitis demonstrated significantly higher bleeding on probing (BOP), plaque index (PI), and gingival index (GI) (P ≤0.002) and a significant drop in BOP, PI, and GI post-treatment (P ≤0.001). Concentrations of MIP-1α and PGE2 were significantly higher (2.8 times) in the gingivitis group than the healthy group (P ≤0.02). After dental prophylaxis, mean biomarker concentrations did not decrease significantly from baseline in the gingivitis group, although concentrations of IL-1β, IL-6, and MMP-8 approached healthy levels, whereas MIP-1α and PGE2 concentrations remained significantly higher than in the healthy group (P ≤0.04). Odds ratio analyses showed that PGE2 concentrations, alone and in combination with MIP-1α, readily discriminated gingivitis from health. CONCLUSIONS Salivary PGE2 and MIP-1α discriminate gingivitis from health, and patients with gingivitis who return to clinical health continue to produce inflammatory mediators for weeks after dental prophylaxis.

In-Office Treatment of Dentinal Hypersensitivity

Dentinal hypersensitivity is a common dental complaint, especially in periodontal patients. It is believed to be mediated by a hydrodynamic mechanism in which various stimuli result in increased fluid flow in dentinal tubules, thereby generating action potentials in associated nerve fibers. Although it is often perceived as mild discomfort by the patient, it can be severe. A variety of interventions has been used, although few have been subjected to rigorous study. This article surveys those in-office treatments that are available, and suggests directions for research so that clinicians may treat patients based on best evidence. Until such evidence is available, it seems prudent to employ therapies that are least likely to cause harm and are reversible.

Smoking and periodontal disease: discrimination of antibody responses to pathogenic and commensal oral bacteria

Smoking is an independent risk factor for the initiation, extent and severity of periodontal disease. This study examined the ability of the host immune system to discriminate commensal oral bacteria from pathogens at mucosal surfaces, i.e. oral cavity. Serum immunoglobulin (Ig)G antibody reactive with three pathogenic and five commensal oral bacteria in 301 current smokers (age range 21–66 years) were examined by enzyme‐linked immunosorbent assay. Clinical features of periodontal health were used as measures of periodontitis. Antibody to the pathogens and salivary cotinine levels were related positively to disease severity; however, the antibody levels were best described by the clinical disease unrelated to the amount of smoking. The data showed a greater immune response to pathogens than commensals that was related specifically to disease extent, and most noted in black males. Significant correlations in individual patient responses to the pathogens and commensals were lost with an increasing extent of periodontitis and serum antibody to the pathogens. Antibody to Porphyromonas gingivalis was particularly distinct with respect to the discriminatory nature of the immune responses in recognizing the pathogens. Antibody responses to selected pathogenic and commensal oral microorganisms differed among racial groups and genders. The antibody response to the pathogens was related to disease severity. The level of antibody to the pathogens, and in particular P. gingivalis, was correlated with disease severity in black and male subsets of patients. The amount of smoking did not appear to impact directly serum antibody levels to these oral bacteria.

Patient-Specific Variations in Biomarkers across Gingivitis and Periodontitis.

This study investigates the use of saliva, as an emerging diagnostic fluid in conjunction with classification techniques to discern biological heterogeneity in clinically labelled gingivitis and periodontitis subjects (80 subjects; 40/group) A battery of classification techniques were investigated as traditional single classifier systems as well as within a novel selective voting ensemble classification approach (SVA) framework. Unlike traditional single classifiers, SVA is shown to reveal patient-specific variations within disease groups, which may be important for identifying proclivity to disease progression or disease stability. Salivary expression profiles of IL-1ß, IL-6, MMP-8, and MIP-1α from 80 patients were analyzed using four classification algorithms (LDA: Linear Discriminant Analysis [LDA], Quadratic Discriminant Analysis [QDA], Naïve Bayes Classifier [NBC] and Support Vector Machines [SVM]) as traditional single classifiers and within the SVA framework (SVA-LDA, SVA-QDA, SVA-NB and SVA-SVM). Our findings demonstrate that performance measures (sensitivity, specificity and accuracy) of traditional classification as single classifier were comparable to that of the SVA counterparts using clinical labels of the samples as ground truth. However, unlike traditional single classifier approaches, the normalized ensemble vote-counts from SVA revealed varying proclivity of the subjects for each of the disease groups. More importantly, the SVA identified a subset of gingivitis and periodontitis samples that demonstrated a biological proclivity commensurate with the other clinical group. This subset was confirmed across SVA-LDA, SVA-QDA, SVA-NB and SVA-SVM. Heatmap visualization of their ensemble sets revealed lack of consensus between these subsets and the rest of the samples within the respective disease groups indicating the unique nature of the patients in these subsets. While the source of variation is not known, the results presented clearly elucidate the need for novel approaches that accommodate inherent heterogeneity and personalized variations within disease groups in diagnostic characterization. The proposed approach falls within the scope of P4 medicine (predictive, preventive, personalized, and participatory) with the ability to identify unique patient profiles that may predict specific disease trajectories and targeted disease management.

Complications when augmenting the posterior maxilla.

The maxillary posterior edentulous region presents a challenge when planning for restoring missing teeth with a dental implant. The available bone in such cases is often not dense and not adequate for the placement of a properly sized implant because of maxillary sinus pneumatization and alveolar bone loss. Maxillary sinus lift is a predictable procedure to provide adequate bone height for the purpose of implant placement. However, complications are encountered during or after the execution of the sinus lift procedure. In this article, the prevention and management of maxillary sinus complications are discussed.

Persistent pain and neurosensory disturbance after dental implant surgery: pathophysiology, etiology, and diagnosis.

Many studies have documented the successful outcomes of dental implants, but have also reported the association of sensory disturbances with the surgical implant procedure. Postsurgical pain is a normal response to tissue injury, and usually resolves after the tissue heals. However, some patients who receive dental implants experience persistent pain even after normal healing. This article describes the basic anatomy and pathophysiology associated with nerve injury. The incidence and diagnosis of these problems, in addition to factors that result in the development of chronic persistent neuropathic pain and sensory disturbances associated with surgical implant placement, are discussed.

Patient-Applied Treatment of Dentinal Hypersensitivity

This article reviews the evidence regarding the effectiveness of various patient-applied interventions for dentinal hypersensitivity. Self-applied treatments are popular because they are both economical and easy to use. The disadvantages include compliance, difficulty to deliver to specific sites, slow onset of action, and the requirement for continuous use. Conflicting research findings make it difficult for the practitioner to determine which self-applied product to advise patients to use. There are a number of issues that have plagued research in this area, including the lack of standardization of stimulus testing and inadequate sample size. The evidence is insufficient to permit the development of evidence-based guidelines for the treatment of dentinal hypersensitivity.

Persistent Pain and Neurosensory Disturbance After Dental Implant Surgery: Prevention and Treatment

Nerve trauma caused by dental implant placement is associated with altered sensation and chronic pain. Complete or partial loss of sensation is often reported by patients who have experienced nerve trauma during implant surgery. Some patients report persistent pain and neurosurgery disturbance long after the normal healing time has passed. In addition, neuropathic pain is reported after implant surgery. Practitioners who place dental implants must be familiar with the differential diagnosis, prevention, and management of neuropathic pain. This article provides insights into the prevention and management of neurosensory deficits and chronic persistent neuropathic pain and considerations for patient referral.