March 17, 2009
The month of March has become synonymous in American culture with the 64-team NCAA men’s basketball tournament, popularly known as March Madness. From Maine to California, millions of Americans this week will stare down the Cinderellas, sleepers, and overwhelming favorites in hopes of choosing the winners of each tournament game from round one to the big championship showdown nearly three weeks later.
But imagine that this year’s March Madness brackets arrived with no names printed in the opening round. Just blanks. In the quarterfinal round, a few of the winners already were named. The same went for the Final Four, and North Carolina and Memphis were a fait accompli to appear in the championship game. Each of these so-called “power” basketball programs – the favorites expected since the start of the season to reach the latter rounds - would serve the same function as biomarkers in health and disease. They would stand out as predictable signs of a predictable outcome. But missing from the narrative would be exactly how the tournament and its 64 variables unfolded over time. Nobody would know about the underdog that came within a whisker of upsetting favorite North Carolina. Nor could anyone fathom that Memphis would have never advanced to the championship game if a rival had not been knocked out of the tournament in an early round.
Such is the case in many ways for the periodontal diseases. Dentists today can easily diagnose the condition in its advanced symptomatic stages; but the subtle opening rounds of infection and inflammation remain mostly a blank molecular diagnostic slate. Greatly needed are informative biomarkers of early, asymptomatic chronic periodontitis that would allow for immediate intervention and change the all-too-predictable outcomes of advanced disease and tooth loss.
This is now beginning to happen for localized aggressive periodontitis (LAP), a leading cause of tooth loss in children, particularly among young African Americans. As reported in the January 2009 issue of the Journal of Periodontology, NIDCR grantees have provided biannual dental exams to a cohort of 96 healthy students (ages 11 to 17) at risk for LAP. Included in this examination is the collection of a saliva sample from each student. When seven students subsequently developed LAP, the scientists examined their saliva samples over the course of the study to evaluate levels of 21 distinct immune system-signaling molecules, or cytokines. Although 19 molecules were not detectable or present at extremely low levels, the scientists found that the cytokine macrophage inflammatory protein-1α (MIP-1α) was quite elevated in the saliva samples of all seven students. In fact, compared to the 21 students who remained LAP free, the levels of the cytokine were 50-fold higher from six to nine months prior to radiographic-detected bone loss, a precursor of tooth loss. Moreover, the increased MIP-1α levels were related to increased probing depth and number of pockets greater than 6 millimeters between tooth and gum, standard measures of advancing periodontal disease. Taken together, the authors suggest that MIP-1ά might be a biomarker of LAP that emerges from pocket sites, makes its way into saliva, and appears to parallel increasing pocket depth before radiographic evidence of bone loss. There is precedent for such an interpretation. In previous studies of the bone cancer multiple myeloma, MIP-1ά was shown to precede radiographic evidence of bone loss by 6 to 12 months. In the current study, MIP-1α had a specificity of 96.8 percent and a sensitivity of 100 percent for bone loss.