Macrophage Inflammatory Protein-1 alpha: 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 actinomy cetemcomitans (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 >= 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)-1 alpha 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)-1 beta was also elevated (P = 0.01). MIP-1 alpha had a specificity of 96.8% and a sensitivity of 100%, whereas IL-1 beta showed 90.3% specificity and 85.7% sensitivity relative to bone loss. MIP-1 alpha levels were also related to increasing probing depth and the number of pockets >6 mm. Conclusion: The superior sensitivity and specificity of MIP-1 alpha, which correlated well with probing depths and the onset of bone loss, suggested that it could be used as an early biomarker for LAgP. J Periodontol 2009;80:106-113.