Macrophage inflammatory protein-1alpha: a salivary biomarker of bone loss in a longitudinal cohort study of children at risk for aggressive periodontal disease?

BACKGROUND: Periodontitis develops in a time-dependent manner. Cross-sectional studies document one moment in time but fail to capture the progressive nature of disease. Radiographic measures of bone loss are relatively insensitive but are reliable markers of irreversible disease. Longitudinal studies are needed to identify biomarkers that can precede radiographic evidence of bone loss and, thus, mark the period prior to clinical evidence of irreversible disease. A longitudinal study of students susceptible to localized aggressive periodontitis (LAgP) was conducted to evaluate chemokines/cytokines found in saliva derived from periodontally healthy children who subsequently developed alveolar bone loss. METHODS: Students were screened, sampled for Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans [Aa]), and divided into a cohort of Aa+ and Aa- students. Ninety-six periodontally healthy Aa+ and Aa- students were recalled every 6 to 9 months following screening. Examinations, saliva collections, and radiographs were performed. After seven students developed bone loss, the levels of 21 cytokines were assessed and matched to saliva from seven Aa+ and seven Aa- students who remained healthy for > or =1 year. Subsequently, saliva from an additional 27 students who remained healthy was analyzed. RESULTS: Nineteen cytokines were not detected or were detected at low levels. Macrophage inflammatory protein (MIP)-1alpha was elevated 50-fold in seven Aa+ students who developed disease 6 to 9 months prior to radiographic detection of bone loss compared to levels in 21 Aa+ and 20 Aa- students who remained healthy (P <0.001). Interleukin (IL)-1beta was also elevated (P = 0.01). MIP-1alpha had a specificity of 96.8% and a sensitivity of 100%, whereas IL-1beta showed 90.3% specificity and 85.7% sensitivity relative to bone loss. MIP-1alpha levels were also related to increasing probing depth and the number of pockets >6 mm. CONCLUSION: The superior sensitivity and specificity of MIP-1alpha, which correlated well with probing depths and the onset of bone loss, suggested that it could be used as an early biomarker for LAgP.

Aggregatibacter actinomycetemcomitans and its relationship to initiation of localized aggressive periodontitis: longitudinal cohort study of initially healthy adolescents.

Aggregatibacter actinomycetemcomitans is frequently associated with localized aggressive periodontitis (LAP); however, longitudinal cohort studies relating A. actinomycetemcomitans to initiation of LAP have not been reported. A periodontal assessment was performed on 1,075 primarily African-American and Hispanic schoolchildren, ages 11 to 17 years. Samples were taken from each child for A. actinomycetemcomitans. A cohort of 96 students was established that included a test group of 38 A. actinomycetemcomitans-positive students (36 periodontally healthy and 2 with periodontal pockets) and 58 healthy A. actinomycetemcomitans-negative controls. All clinical and microbiological procedures were repeated at 6-month intervals. Bitewing radiographs were taken annually for definitive diagnosis of LAP. At the initial examination, clinical probing attachment measurements indicated that 1.2% of students had LAP, while 13.7% carried A. actinomycetemcomitans, including 16.7% of African-American and 11% of Hispanic students (P = 0.001, chi-square test). A. actinomycetemcomitans serotypes a, b, and c were equally distributed among African-Americans; Hispanic students harbored predominantly serotype c (P = 0.05, chi-square test). In the longitudinal phase, survival analysis was performed to determine whether A. actinomycetemcomitans-positive as compared to A. actinomycetemcomitans-negative students remained healthy ("survived") or progressed to disease with attachment loss of >2 mm or bone loss (failed to "survive"). Students without A. actinomycetemcomitans at baseline had a significantly greater chance to remain healthy (survive) compared to the A. actinomycetemcomitans-positive test group (P = 0.0001). Eight of 38 A. actinomycetemcomitans-positive and none of 58 A. actinomycetemcomitans-negative students showed bone loss (P = 0.01). A. actinomycetemcomitans serotype did not appear to influence survival. These findings suggest that detection of A. actinomycetemcomitans in periodontally healthy children can serve as a risk marker for initiation of LAP.