Bisphosphonates and osteonecrosis of the jaw: proceedings of an international conference.

There has been an upsurge of multidisciplinary research since the adoption of a standardized definition of osteonecrosis of the jaw (ONJ) and the first bisphosphenate-related ONJ conference in 2007 held at the New York Academy of Sciences. This series of papers revisits topics presented at the conference in addition to covering recent advances in the history, mechanisms, clinical management, and prevention of bisphosphonate-related ONJ.

Plasma levels of tumour necrosis factor-alpha in patients with chronic periodontitis and type 2 diabetes.

OBJECTIVES: Studies suggest that elevated circulating tumour necrosis factor-alpha (TNF-alpha) may contribute to insulin resistance in patients with type 2 diabetes. The source of plasma TNF has been thought to be adipocytes associated with obesity, but inflammation and infection result in TNF-alpha production as well. METHODS: We studied 46 patients with type 2 diabetes and chronic periodontitis to determine the relationship between plasma TNF-alpha levels and clinical measures of periodontitis, gingival crevicular fluid (GCF) interleukin-1beta (IL-1beta), plasma endotoxin, serum glucose, and glycated haemoglobin (HbA1c). TNF-alpha levels were measured using a high sensitivity enzyme-linked immunosorbent assay. RESULTS: TNF-alpha showed a significant positive correlation with attachment loss (r=0.40, p=0.009), plasma endotoxin (r=0.33, p=0.03), and GCF IL-1beta (r=0.33, p=0.035), but not probing depth (r=0.28, p=0.07), bleeding on probing (r=0.30, p=0.053), plaque index (r=0.22, p=0.17), serum glucose, HbA1c (r=0.10, p=0.50), or body mass index (r=0.077, p=0.62). A dose-response relationship was observed between periodontitis severity and TNF-alpha (p=0.012). CONCLUSION: The finding that chronic periodontitis is associated with plasma TNF-alpha levels in subjects with type 2 diabetes supports the hypothesis that periodontal infection and inflammation may contribute to insulin resistance.

Analysis of multiple 2x2 tables with site-specific periodontal data.

Periodontal data typically consist of observations made at multiple sites within each patient. Observations within a patient tend to be positively correlated; hence, standard statistical techniques that assume independence are invalid. Regression techniques for correlated data have been proposed; communicating results from these models, however, is difficult, due to their inherent complexity. Simpler statistical approaches have also been proposed, but many of these methods can be applied only when covariates are specific to the subject, and do not vary from site to site within a subject. In this paper, we present two methods for the analysis of multiple 2x2 tables containing site-specific periodontal data. The methods presented are modifications of the well-known Mantel-Haenszel methods. We illustrate these methods using a subset of data from a clinical trial examining the effects of scaling and root planing on levels of interleukin-1 beta.

Changes in gingival crevicular fluid levels of immunoglobulin A following therapy: association with attachment loss.

BACKGROUND: In previous studies, we demonstrated that increased levels of immunoglobulin A (IgA) in gingival crevicular fluid (GCF) may be "protective", while increased levels of the polymorphonuclear lysosomal enzyme, beta-glucuronidase, in GCF were associated with increased risk of disease activity. In this study, we examined the effect of scaling and root planing (SRP) on the levels of beta-glucuronidase, IgG, and IgA in GCF over a 24-week period and compared these to clinical attachment loss (CAL). METHODS: Twenty-nine patients with periodontal disease were examined for attachment level, probing depth, plaque, and bleeding on probing at 6 sites per tooth. GCF was collected from the mesial aspect of all teeth excluding third molars and analyzed for beta-glucuronidase, IgG, and IgA. After baseline data were collected, each patient received SRP, and GCF was collected again at 2, 4, 6, 8, 12, and 24 weeks post-SRP while clinical data were obtained at 4, 8, 12, and 24 weeks. In addition, we analyzed whether the magnitude of the IgA response to SRP would affect the rate of periodontal disease progression by examining GCF IgA levels at 2 time intervals: 2 to 4 weeks post-SRP and 6 to 12 weeks post-SRP. RESULTS: Seventeen patients (58.6%) exhibited at least 1 site losing > or =2.5 mm of CAL during the 24-week study. Beta-glucuronidase in GCF was significantly decreased at 2 weeks following SRP and then demonstrated a gradual increase throughout the study period. Levels of IgA in GCF significantly increased following SRP, reaching a peak at 6 weeks and then gradually decreasing throughout the study. Furthermore, we found an inverse relationship between GCF IgA levels at 6 to 12 weeks post-SRP and the occurrence of CAL. CONCLUSIONS: These results support the hypothesis that maintenance of high levels of IgA in GCF may be "protective" against periodontal attachment loss. Furthermore, levels of beta-glucuronidase appear to be a more sensitive indicator of gingival inflammation than clinical measures.

Interleukin-1beta and beta-glucuronidase in gingival crevicular fluid from molars during rapid palatal expansion.

This study examined whether the inflammatory mediators interleukin (IL-1beta) and beta-glucuronidase (betaG) are present in the gingival crevicular fluid (GCF) of children undergoing rapid palatal expansion and whether their levels vary upon activation of the appliance and movement of the maxillary first molars. Nine adolescent patients who needed palatal expansion were studied. Each patient received a periodontal prophylaxis and instruction in proper home care, including rinsing with chlorhexidine. Four weeks later, a modified Hyrax appliance was inserted. The jackscrew was activated twice daily until the appropriate expansion was achieved. GCF samples were collected at 2 pretreatment observation periods and 9 observation periods after placement of the appliance. Samples were collected with filter paper strips and analyzed by means of ELISA and time-dependent fluorometry for IL-1beta and betaG, respectively. The values recorded at the observation period 2 weeks after the periodontal prophylaxis were used as baseline. Paired t tests were used to compare mediator levels at this baseline to the levels obtained at each of the subsequent observations. The results indicate that (1) betaG and IL-1beta are present in GCF of young, healthy individuals, (2) their levels decrease following a strict regimen of plaque control, (3) orthodontic/orthopedic forces evoke changes in the levels of the inflammatory mediators IL-1beta and betaG in the periodontal tissues that can be detected in GCF. The results of this study support the hypothesis that mechanical stimulus causes an inflammatory reaction within the periodontal tissues, which in turn may trigger the biological processes associated with bone remodeling.

New concepts regarding the pathogenesis of periodontal disease in HIV infection.

Periodontal manifestations of human immunodeficiency virus (HIV) infection were first described in 1987. Initially, the lesions receiving attention were HIV-associated gingivitis (now known as linear gingival erythema [LGE]) and HIV-associated periodontitis (now known as necrotizing ulcerative periodontitis [NUP]). The true prevalence of LGE was difficult to determine due to variable diagnostic criteria. Recently, LGE has been associated with intraoral Candida infection. The prevalence of NUP is low (< or = 5%), and this lesion is associated with pronounced immunosuppression. Current focus on the periodontal manifestations of HIV infection centers on rapid progression of chronic adult periodontitis in HIV+ patients. Attempts to identify the pathogenesis of the increased progression of periodontitis have not proven successful. For example, analysis of subgingival plaque for the presence of bacterial pathogens has failed to detect differences between HIV+ and HIV- patients. Recently our laboratory has identified alterations in the host response in the gingival crevice of HIV+ patients. Comparing HIV+ and HIV- injecting drug users (IDU), levels of the proinflammatory cytokine interleukin-1 beta (IL-1 beta) in gingival crevicular fluid (GCF) were slightly elevated at sites with a probing depth of 1 to 3 mm. At deeper sites (> or = 4 mm), total IL-1 beta in GCF was significantly greater in HIV+ individuals. Using the lysosomal acid glycohydrolase beta-glucuronidase (beta G) as a measure of the influx of polymorphonuclear leukocytes (PMN) into the gingival crevice, our data indicated a significant correlation of total beta G in GCF and probing depth in the HIV-IDU (r = 76; P = .02). This result was similar to what we have observed in other studies. In contrast, for HIV+ subjects, total beta G was not associated with probing depth (r = .20; NS). These data suggest that HIV+ patients have altered regulation of PMN recruitment into the gingival crevice. We have begun to investigate the conditions under which subgingival Candida may contribute total periodontal lesions in HIV+ individuals. Candida from subgingival sites has been cultured in HIV+ individuals. Subgingival Candida was distinct from Candida isolated from tongue and buccal mucosal surfaces (as indicated by genomic fingerprinting). We hypothesize the absence of adequate priming of PMN by HIV+ patients. This may be due to a reduced Th1 lymphocyte response. The inability of HIV+ individuals to adequately prime PMN may allow Candida to colonize the subgingival environment. In that milieu, it may act directly or in concert with subgingival bacterial pathogens, or as a cofactor (by inducing production of proinflammatory cytokines) to increase the occurrence of periodontal attachment loss.

Serum IgG antibody response to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis: implications for periodontal diagnosis.

The relationship of the serum antibody titer and avidity to the putative periodontal pathogens Actinobacillus actinomycetemcomitans (Aa) strains Y4 and 29523 and Porphyromonas gingivalis (Pg) strain 381 were examined in relation to clinical parameters in 26 gingivitis and 28 periodontitis patients. The relationship of antibody titer and avidity to infection with the homologous organism was also examined in a subset of 30 patients. Antibody titer was determined by an enzyme-linked immunosorbent assay, and antibody avidity was assessed using a dissociation assay. Considering all patients, there was a significant negative correlation between mean probing depth and antibody titer (r=-0.28) and avidity (r=-0.28) to Aa Y4. There was a significant positive correlation of probing depth and antibody titer (r=0.46) and avidity (r=0.46) to Pg. The correlation of antibody titer and avidity to Aa and infection with Aa Y4 (r=-0.32, r=-0.21) and Aa 29523 (r=-0.35, r=-0.39) was negative, while the correlations of titer and avidity to Pg and presence of the organisms was strongly positive (r=0.40, r=0.35). These data indicate that the relationship of serum antibody titer and avidity to clinical parameters of periodontal disease severity and the level of infection with the homologous organism appears to be different for Aa and Pg. The development of an antibody response to Aa appears to protect the individual from infection with the organism. In contrast, the development of an antibody response to Pg was not able to eliminate the infection. These results should be considered when developing a diagnostic strategy for periodontal disease utilizing the humoral immune response.

Epidemiology and diagnosis of HIV-associated periodontal diseases.

A review of periodontal disease as a manifestation of HIV infection suggests a shift in emphasis over the past 5 years. Initially the focus was on newly described forms of periodontal disease (i.e., HIV-associated gingivitis or linear gingival erythema (LGE); HIV-associated periodontitis or necrotizing ulcerative periodontitis (NUP). While the clinical definition of LGE varies from study to study, an association between LGE and Candida infection has been described. Furthermore, the prevalence of NUP is quite low and this disorder is associated with severe immunosuppression. In contrast, the focus today is on the accelerated rate of chronic adult periodontitis occurring in seropositive patients. While the organisms that characterize adult periodontitis in seronegative individuals are present in subgingival plaque from seropositive individuals, reports suggest that atypical pathogens are also present (i.e., Mycoplasma salivarium, Enterobacter cloacae). Recent studies from our laboratory have identified a novel strain of Clostridium isolated from the subgingival plaque of injecting drug users that has pathologic potential. This organism, however, was found in both seropositive and seronegative individuals in this cohort, suggesting an association with lifestyle rather than serostatus. In addition, data has been published examining the local host response in periodontitis in seropositive individuals. Distinctly elevated levels of IgG in gingival crevicular fluid (GCF) have been observed in seropositive patients. Furthermore, data from our laboratory examining inflammatory mediators in GCF (polymorphonuclear leukocyte lysosomal enzyme beta-glucuronidase and the pro-inflammatory cytokine interleukin-1 beta) suggests an altered response in patients with HIV infection. The alteration manifests as the absence of the expected strong correlation between polymorphonuclear leukocyte activity in the gingival crevice and clinical measures of existing periodontal disease, as well as elevated levels of interleukin-1 beta in sites with deeper probing depths. Therefore, it can be concluded that the progression of periodontal disease in the presence of HIV infection is dependent upon the immunologic competency of the host as well as the local inflammatory response to typical and atypical subgingival microorganisms.

Inflammatory and immune mediators in crevicular fluid from HIV-infected injecting drug users.

Gingival crevicular fluid (GCF) levels of the polymorphonuclear leukocyte (PMN) lysosomal enzyme beta-glucuronidase (beta G), the pro-inflammatory cytokine interleukin 1 beta (IL-1 beta), and immunoglobulins (IgA, IgG, and IgM) were examined in 16 HIV seropositive (HIV+) and 10 HIV seronegative (HIV-) injecting drug users (IDU). Each subject received a periodontal examination including assessment of probing depth, attachment level, bleeding on probing, and plaque and calculus accumulation. GCF was collected from the mesial surfaces of premolar and molar teeth using filter paper strips. Although HIV+ subjects had a significantly lower number of peripheral blood CD4+ T cells/mm3 compared to HIV- subjects, there were no significant differences in mean probing depth, percentage of sites exhibiting bleeding on probing, or plaque and calculus accumulation between HIV- and HIV+ subjects. When the GCF components were analyzed, we found no significant differences between HIV- and HIV+ subjects in GCF levels of beta G, IL-1 beta, IgA or IgM, but GCF levels of IgG were significantly increased in HIV+ subjects. When sites were categorized by probing depth, no differences in the levels of beta G, IgA, IgG, and IgM existed between sites with probing depth < or = 3 mm compared to sites with probing depth > or = 4 mm in both HIV- and HIV+ IDU. However, levels of IL-1 beta in GCF were increased in the deeper sites (> or = 4 mm) in HIV+ IDU when compared to sites with PD < or = 3 mm. Analyzing GCF constituents in relation to the CD4 cell number, no differences were found between subjects with < or = 400 or > 400 CD4 cells/mm3 with respect to the levels of IL-1 beta, IgG, and IgM. However, the level beta G was significantly decreased in the HIV+ IDU with < or = 400 CD4 cells when compared to those with > 400 CD4 cells/mm3, while levels of IgA were significantly higher in HIV+ subjects with < or = 400 CD4 cells/mm3. Our results suggest that levels of IgG, and in immunodeficient subjects IgA were increased in GCF of HIV+ IDU while decreased levels of beta G were found in immunodeficient HIV+ IDU. These findings may be local manifestations of systemic alterations and suggest that analysis of GCF may provide insight into the immune and inflammatory responses of HIV-infected individuals to periodontal microorganisms.

Interleukin-8 and beta-glucuronidase in gingival crevicular fluid.

Polymorphonuclear leukocytes (PMN) play a critical role in the host's response to the subgingival microflora. Interleukin-8 (IL-8) is a potent chemotactic and activating factor for PMN. In this study, the presence of IL-8 in gingival crevicular fluid (GCF) was examined in relation to the PMN indicator beta-glucuronidase (beta G), as well as clinical parameters of chronic inflammatory periodontal disease. Data was obtained from 30 patients with periodontitis and 14 healthy controls. For the control group, GCF and clinical data were obtained only once. For the periodontitis patients, clinical data and GCF samples were collected prior to treatment, and GCF samples were again collected 2 weeks after scaling and root planing. Comparing control and periodontitis patients prior to treatment, IL-8 concentration was lower in the patients with periodontitis. Scaling and root planing resulted in either an increase or a decrease in total IL-8 and IL-8 concentration GCF. A reduction in total IL-8 or IL-8 concentration was accompanied by a corresponding reduction in beta G activity. An increase in total IL-8 or IL-8 concentration after scaling and root planing was associated with an increase in beta G activity in some patients and a reduction in beta G activity in other patients. The periodontitis patients who did not demonstrate a linkage between IL-8 and beta G activity in GCF were those individuals with the highest beta G activity prior to treatment. As elevated beta G activity in GCF has been associated with an increased risk for probing attachment loss, the absence of a direct relationship between IL-8 in GCF and PMN recruitment into the gingival crevice may characterize individuals at risk for progression of periodontitis.

Oral manifestations of HIV infection.

The oral manifestations of HIV infection are reviewed along with evidence supporting the need for training of health-care professionals in the recognition of oral lesions. The diagnosis, prevalence, pathogenesis, and management of the most common oral lesions observed in HIV infection are described. Oral candidiasis and hairy leukoplakia are two oral lesions that have been demonstrated to have important prognostic significance. The diagnosis and management of periodontal disease in seropositive patients is emphasized, and a preventive protocol for patients at risk for periodontal pathology is recommended.

A prospective study of oral lesions and their predictive value for progression of HIV disease.

OBJECTIVE: This report evaluates and compares individual oral lesions and combinations of lesions in predicting progression-free survival in a seroprevalent cohort of men and women with HIV infection. DESIGN: This was a prospective study of HIV-infected patients, initially AIDS-free, followed for approximately 30 months. SETTING: Patients were volunteers examined at an academic medical center and at an inner-city hospital in New York. Participants identified themselves as homosexual men or as injection drug users (IDU). OUTCOME MEASURES: The primary outcome being assessed is time from a baseline oral examination until the development of an AIDS-defining condition or death from any cause within 12 months of the last study visit. Correlation is measured by relative risk (RR). RESULTS: While oral lesions were not predictive of progression among subjects with CD4 > or = 200, they were highly predictive of progression among those with CD4 < 200. For subjects with CD4 < 200, the only individual lesion that was significantly associated with progression-free survival was oral candidiasis (RR = 4.12, P = 0.009). Positivity for one or more lesions in a set demonstrated greater prognostic value among those with CD4 < 200, with RR's of 6.03 (P = 0.018) for the set consisting of oral candidiasis, hairy leukoplakia, and necrotizing ulcerative gingivitis (NUG), and 8.77 (P = 0.036) for the set consisting of the above lesions plus linear gingival erythema (LGE). Analysis by cohort suggested that the improvement in correlation was stronger in homosexual men than in IDU, but this question could not be resolved conclusively with these data. CONCLUSIONS: Lesion sets might be better prognosticators of progression-free survival than individual lesions among HIV-infected subjects with CD4 < 200. Prognostic value of the core lesion set (oral candidiasis and hairy leukoplakia) was enhanced by the addition of other lesions (NUG and LGE) not usually included in HIV staging systems. These results suggest that staging systems for HIV might be improved by the inclusion of other, survival-related oral lesions.

The effect of tetracycline fiber therapy on beta-glucuronidase and interleukin-1 beta in crevicular fluid.

Treatment with the tetracycline HCL-containing (Actisite infinity) fiber has been shown to improve clinical measures of periodontitis, as well as reduce the number of sites infected with putative periodontal pathogens. In this study, we examined the effect of the tetracycline fiber on biochemical mediators of the host's inflammatory response in gingival crevicular fluid (GCF). The total amount of the lysosomal enzyme beta-glucuronidase (beta G), considered a marker of primary granule release from polymorphonuclear leukocytes and interleukin-1 beta, a cytokine with important proinflammatory effects, were examined in GCF. Patients with localized recurrent periodontitis were followed over a 16 week period. Treated teeth (Tx), teeth adjacent to treated teeth (ADJ) and control teeth (Cx) were studied. Following fiber therapy, the Tx teeth displayed statistically significant reductions in mean probing depth, depth of the deepest site and bleeding on probing over the 16 weeks of the trial. Significant reduction in the depth of the deepest site was also seen for the ADJ teeth over 16 weeks. Total beta G in GCF was reduced for the Tx teeth comparing baseline to 16 weeks, but no significant changes were observed for the ADJ or Cx teeth. Prior to treatment, total beta G for the Tx teeth was 211 +/- 49 U (mean +/- standard error), versus 146 +/- 174 U for the ADJ teeth and 121 +/- 33 U for the Cx teeth. 16 weeks treatment, the mean values for these 3 categories of teeth were comparable (Tx = 95 +/- 20 U, ADJ = 93 +/- 42 U and Cx = 103 +/- 29 U). For the Tx teeth, the maximum reduction in total beta G following therapy occurred at 6 weeks (65%). Total IL-1 beta was significantly reduced for the Tx teeth at 3 and 6 weeks, but rebounded at 16 weeks. In contrast to what was seen for beta G, the maximum reduction in total IL-1 beta for the Tx teeth was observed at 3 weeks (68%). These data suggest that host mediators associated with increased risk for active disease are reduced following tetracycline fiber therapy. Future studies will determine the relative importance of a reduced microbial challenge versus a tetracycline-mediated direct modification of the host response to account for the reduction in the host inflammatory response in GCF following tetracycline fiber therapy.

Prevalence of antibodies to rickettsiae in the north-western part of Bosnia and Herzegovina.

The prevalence of rickettsial antibodies in north-western part of Bosnia and Herzegovina was studied. Among 231 sera tested by complement fixation (CF) positive were: 61.5% for Rickettsia typhi, 4.3% for R. prowazekii, 1.7% for R. conorii and 19.0% for Coxiella burnetii. Of 183 sera tested by indirect immunofluorescence assay (IFA) 37.7% reacted with R. typhi, 1.6% with R. conorii and 22.4% with C. burnetii. The results show that at least R. typhi and C. burnetii are highly endemic in this area.

The relationship of candidiasis to linear gingival erythema in HIV-infected homosexual men and parenteral drug users.

Periodontal status was evaluated in two cohorts participating in a study of the natural history of human immunodeficiency virus (HIV) infection. One cohort consisted of 77 seropositive and 44 seronegative homosexual men, and the other cohort was comprised of 44 seropositive and 39 seronegative parenteral drug users (PDU). No differences were observed between seropositive and seronegative individuals within a cohort in terms of clinical periodontal parameters (percent of sites with > or = 4 mm probing depth, percent of sites exhibiting bleeding on probing, mean oral hygiene index). The PDU displayed more existing periodontal disease than the homosexual men. Periodontal disease in the seropositive individuals in both cohorts was not strictly related to the number of CD4+ lymphocytes. Linear gingival erythema (LGE), defined as an erythematous band of at least 2 mm extending between adjacent papilla, was observed in all 4 groups. Seropositive homosexual men displayed more LGE than seronegative homosexual men (16.6% vs. 11.4%) and seronegative PDU displayed more LGE than seropositive PDU (38.5% vs. 29.5%), but neither difference was significant. LGE tended to be related to reduced numbers of CD4+ lymphocytes, but this relationship did not reach statistical significance. A statistically-significant relationship was found between the presence of intraoral candidiasis and LGE in seropositive homosexual men: 42.9% of these subjects with candidiasis had LGE, while only 12.7% of the subjects without candidiasis had LGE (P < .05). For the seropositive PDU, 35.3% of the individuals with candidiasis had LGE and 25.9% of the subjects without candidiasis displayed LGE, but the difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoglobulin isotypes in gingival crevicular fluid: possible protective role of IgA.

In order to simultaneously assess the local humoral immune and polymorphonuclear leukocyte (PMN) responses in periodontal disease, IgG, IgM, and IgA, as well as the PMN lysosomal enzyme beta-glucuronidase (beta G), were examined in gingival crevicular fluid (GCF) from patients with varying degrees of periodontal pathology. Evaluations were made before and after conservative therapy (scaling and root planing). Thirty patients with varying degrees of periodontal pathology, ranging from mild inflammatory gingivitis to moderate periodontitis, were studied. GCF was collected from the mesial surfaces of all teeth. The presence of the 3 immunoglobulin isotypes was determined by enzyme linked immunosorbent assays (ELISA), while total beta G activity in GCF was determined by a fluorometric assay. Clinical parameters were obtained from 6 sites per tooth. Our data indicate that prior to treatment, total beta G activity is strongly related to the severity of periodontal disease as measured by mean probing attachment level (AL; r = 0.89; P < .005), mean probing depth (PD; 4 = 0.89; P < .0005) and percentage of sites exhibiting bleeding on probing (% BOP; r = 0.49; P < .005). Following treatment, no statistically significant relationship of disease severity and beta G is found. The concentrations of IgG and IgM in GCF do not follow a specific pattern when related to disease severity. In contrast, prior to treatment the concentration of IgA is negatively correlated to mean AL (r = -0.54; P < .005), mean PD (r = -0.59; P < .005), and % BOP (r = -0.47, P < .005).(ABSTRACT TRUNCATED AT 250 WORDS)

Oral manifestations of HIV infection in homosexual men and intravenous drug users. Study design and relationship of epidemiologic, clinical, and immunologic parameters to oral lesions.

This article describes the baseline findings from a study designed to compare the oral manifestations of HIV infection in homosexual men and intravenous drug users. Both seropositive and seronegative persons were studied. A standard examination instrument was developed to record indexes of oral disease as well as to record the presence of oral lesions. The two groups differed in terms of education, race, socioeconomic status, employment status, housing, and smoking experience. The prevalence and type of oral lesions differed in the two seropositive groups. In seropositive homosexual men, white lesions on the tongue (28.4%) predominated; whereas for the seropositive intravenous drug users, oral candidiasis (43.0%) and gingival marginal erythema (33.3%) were most often detected. We also observed that seronegative intravenous drug users displayed a greater number of oral lesions than seronegative homosexual men. For seropositive homosexual men, lesion presence was significantly associated with decreased levels of CD4; positive associations were seen with current smoking, antiviral drug use, and antibiotic use, and a negative association was observed with current employment. In contrast, only exposure to antiviral drugs was significantly correlated with lesion presence for seropositive intravenous drug users. This baseline analysis from our longitudinal study suggests clear differences in oral manifestations of HIV infection between seropositive homosexual men and intravenous drug users and between seronegative homosexual men and intravenous drug users. Among other parameters, it is apparent that lifestyle, access to health care, and the condition of the oral cavity before infection influence the development of oral lesions in persons with HIV infection.

Development of a risk profile for periodontal disease: microbial and host response factors.

Advances in our understanding of the relationship between the microbial challenge and the host response in periodontal disease have led to the search for pathogenesis-based risk indicators or risk factors for disease progression. This evaluation is based on analysis of non-invasive or minimally invasive samples that allow measurement of the subgingival plaque microflora or the host response in gingival crevicular fluid (GCF), serum, or saliva. Studies conducted by us have indicated that in GCF, persistently elevated levels of beta-glucuronidase (beta G, a marker for primary granule release from polymorphonuclear leukocytes) are associated with clinical attachment loss in patients with periodontitis. This finding has been confirmed in a multicenter trial. We have also observed that a statistically significant positive correlation exists between beta G in GCF and measures of the subgingival microbial challenge, but the correlation was less than 0.5, suggesting variations in the host response to the challenge. Furthermore, beta G levels in GCF were inversely correlated with the IgG serum antibody titer to a panel of periodontal pathogens, suggesting the essentially protective function of the systemic humoral response in periodontal disease. Data in the literature support this concept. In addition, recent studies of the relationship of antibody isotypes in GCF to progression of clinical attachment loss have suggested that IgA in GCF has a protective function. This may relate to the lack of complement activation by IgA. Alternately, the development of IgA antigen-specific responses are T-cell dependent, and reductions in local levels of IgA may indicate a decrease in T-helper cell function. These data have allowed development of strategies for identifying individual risk profiles for patients with periodontal disease based on the host response to the microbial challenge. With identification of these risk indicators/risk factors for active periodontal disease, the next challenge is to provide clinicians with access to the tests and analyses that are required for this approach to periodontal diagnosis. Improved patient management should result from the incorporation of these tests into clinical practice.