Periodontology’s One-Of-A-Kind Citation Classic

Exp Gingivitis

As has been mentioned, the American Academy of Periodontology celebrates in 2014 her centennial. On that auspicious occasion, several themes which have shaped modern Periodontology have been identified by the Editor-in-Chief, and prominent opinion leaders asked to give brief summaries on each. The first commentary on “Bacteria [that] Play a Critical Role in the Etiology of Periodontal Disease” by Professor Niklaus P. Lang 2014 has just appeared in the February issue of the Journal of Periodontology. The title is remarkably conservative, avoiding any claims as regards periodontal diseases’ “causes”.

The brief digest summarized fifty years of oral microbiology as regards periodontal research, mentioning ground-breaking work by the Socransky group in Boston, MA; Slots in Copenhagen and later Buffalo, NY, together with Genco; as well as Loesche in Ann Arbor, MI; and Moore and Holdeman-Moore in Richmond, VA. But it also quickly focuses, in a couple of paragraphs, on the famous study on Experimental Gingivitis in Man of 1965 by one of the most eminent Norwegian periodontists, Harald Löe. Right now, the paper has been cited 2533 times, while its set-up has been repeated several hundred times for different research questions. Lang explains,

“It [the Experimental Gingivitis in Man paper] reported a straightforward, hypothesis-driven clinical experiment with only 12 volunteers, and it asked the question: Would the amount of plaque mass buildup on the teeth result in gingivitis?

During a 3-week period of no oral hygiene, all volunteers predictably developed generalized gingivitis, and upon reinstitution of oral hygiene practices, they returned to pre-experimental low levels of plaque and gingivitis. Some of the power of this study came from unique and innovative design features, including the use of healthy young human volunteers with no systemic diseases, no malnutrition, and no occlusal trauma. In addition, the participants were their own controls, so they were all taken to a healthy gingival status at baseline, induced to gingivitis solely by the absence of oral hygiene, and then returned to health solely by reinstitution of oral hygiene.”

It is worth to revisit the paper by Löe et al. (1965) after almost 40 years. Nine first-year clinical students, one teacher in Periodontology and two laboratory technicians participated in a clinical and microbiological experiment. There was no mention as regards health or occlusion. At first exam they had low, but not zero, Plaque Index (PI) scores (means between 0.00 and 0.95), which had been described the year before by Silness and Löe (1964) and low, but not zero (0.02-0.69), Gingival Index (GI) scores (Löe and Silness 1963). Although throughout scores on altogether one thousand gingival units, as the authors mention, were considered which were, according to Lang (2014) “well-defined”, Löe et al. (1965) generally averaged scores at the tooth level, groups of teeth, the area level, the subject level and the cohort level. Thus, fractions of an integer (for instance 0.60) have to be interpreted as frequencies of scores (e.g., 40% score 0, 60% score 1), since only scores were “well defined”. There was actually no preparatory phase when plaque and gingival inflammations was brought to zero. Participants, who were consistently called “patients” in the paper, withdraw from all oral hygiene and were “rechecked at varying time intervals, and a full assessment of their plaque and gingival status was carried out each time using the same  criteria at the introductory eaxmination. As soon as inflammatory changes were observed and a complete index and bacteriological assessment had been made, the patients were given detailed instructions in oral hygiene methods using brush and wood massage sticks.” “At a point where the GI and PI scores approached zero, the experiment was terminated.”

It is not so clear when oral hygiene was re-instituted. All participants presented with some inflammation already at the outset. Authors describe, “In the course of the ‘no-brushing’ part of the experiment all the subjects developed gingivitis. The mean Gingival Index increased from 0.27 to just 1.05. Three subjects developed gingivitis within ten days, whereas nine subjects took between fifteen and twenty-one days.” During the no-brushing period, average Plaque index rose from 0.43 to 1.67. Fortunately, “After recommencement of tooth cleansing, gingivalk inflammation resolved in about a week, during which the mean GI for the whole group dropped from 1.05 to 0.11,” when mean PI was 0.17. As regards microbiological (microscopic) observations, Löe et al. (1965) summarize,

“The bacteriological examinations have clearly shown that essential changes occur in the bacterial flora of the gingival margin during the period of plaque development. The number of microorganisms colonizing a clean and healthy gingiva is low and the flora consists almost entirely of grampositive cocci and short rods. During plaque formation a general increase in the number of microorganisms takes place, and in the course of a few days a definite change in the composition of the flora occurs. From a predominance of coccal forms the microflora changes to a more complex population in which first filamentous bacteria, and later vibrios, spirochetes and gram-negative cocci are prominent.”

Lang (2014) stresses that,

“There are not many diseases for which such a perfect cause-and-effect relationship, as the one of amount of bacterial plaque and experimental gingivitis, has been established. The results were communicated with figures and a simple message that were powerfully clear to every reader.”

Well, whether Löe et al. (1965) had even observed development of a disease had been controversial over the years. The described inflammation with a Gingival Index score of about 1 (the index ranges from 0 to 3) is not related to gingival bleeding, and Lang et al. (1990) have later reported that absence of gingival bleeding (following active periodontal therapy) is in fact associated with periodontal stability. Löe has tried later to justify his stark opinion that mild gingivitis must be considered a disease which inevitably leads to periodontal distruction if not prevented or treated in many other studies. Most recently, Hujoel wrote, in 2009 in a highly recommended chapter of a statistical textbook on evidence and frequent lack thereof in Dentistry,

“No pivotal cohort study identified infection as the cause of destructive periodontal disease. One citation classic in support of the periodontal infection theory is a case-series of nine dental students, a dental professor, and two dental technicians who brought their gingiva to an unnatural inflammation-free condition referred to as ‘Aarhus superhealthy gingiva’ (Theilade, 1987), and then subsequently stopped brushing their teeth (Löe et al., 1965). The experimental gingivitis that developed in ten to twenty days formed ‘didactic proof of the essential role of dental plaque bacteria in periodontal diseases’ (Theilade 1987). Findings on acute experimental gingivitis were extrapolated to chronic clinical gingivitis, and – a huge leap – to periodontal diseases.” (Emphasis as such.)

A few years later Hujoel et al. (2013) had pointed to the lack of evidence that certain bacterial species are causally associated with destructive periodontitis. They provocatively stress that, “Given this absence of evidence, it is unclear why it became ‘virtually sacrilegious’ to question why destructive periodontal disease became defined as an infectious disease.”

Before we accept that periodontal disease is caused by certain bacteria (and Lang is wise not to claim that already in the title of his commentary), smoking tobacco and low socio-economic status must be considered as well. In order to prevent periodontitis in a population, it would be most promising to seriously address both factors. There is most probably not “a limited number of periodontal pathogens” associated with the onset and progression of periodontitis. Oral hygiene may have improved over the year due to lifestyle changes. That could not, however, reduce periodontitis morbidity over the years as the new  U.S. data [pdf] has shown.

7 February 2014 @ 7:18 pm.

Last modified July 8, 2014.


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