Commentary

A Ninety-Year History of Periodontosis: The Legacy ofProfessor Bernhard Gottlieb

Daniel H. Fine,* D. Walter Cohen,† Enrique Bimstein,‡ and Corinna Bruckmann§

This commentary is intended to: 1) honorGottlieb’s discovery of ‘‘periodontosis;’’ 2)‘‘review Gottlieb’s influence on our under-

standing of periodontal pathogenesis’’; and 3)stimulate interest in unresolved questions.

THE SCHOLAR

Bernhard Gottlieb was born in 1885 and received hismedical degree from the University of Vienna in 1911.1

He chose dentistry as his area of specialization and,along with a group of colleagues under his tutelage,explored areas of oral biology that had a marked in-fluence in the fields of endodontics, orthodontics,periodontics, and cariology.1,2 He was instrumental informing and leading a group of research scientistsknown as the Vienna Dental Group, which consistedof Orban, Sicher, Kronfeld, Weinmann, and Gottlieb.2 Thecontributions made by this group of clinical scientistshas resulted in the foundation of the understanding ofhealth and disease with respect to the biology andpathology of teeth and their supporting tissues.1,2 Heis credited by some as the first to integrate basicscience information into clinical treatment in thepractice of dentistry.3 For the most part, studiesconducted by the group took place at the AnatomicInstitute of Vienna. Gottlieb’s international recogni-tion came as a result of the meticulous histologicpreparations of human jaws he examined that wereobtained fromAustrian soldiers killed inWorld War I.2

The histology highlighted resorptive processes in-volving both alveolar bone and root. Gottlieb directedstudies in all areas of dentistry, but his main focuswas on the study of periodontal disease. One of his

first publications to gain major attention was titled,‘‘Etiology and Therapy of Pyorrhea Alveolaris.’’4

THE DISCOVERY

During Gottlieb’s era, diseases were categorized asinflammatory, dystrophic, or neoplastic.5 In a 1923publication, Gottlieb presented material from anunusual form of periodontal disease he discovered inhis autopsy material that he called ‘‘diffuse alveolar

Figure 1.Professor Bernhard Gottlieb, circa 1940.

* Department of Oral Biology, School of Dental Medicine, Graduate Schoolof Biomedical Sciences, Rutgers University, New Brunswick, NJ.

† Drexel University College of Medicine, Philadelphia, PA.‡ Pediatric Dentistry, University of Kentucky College of Dentistry, Lexington,KY.

§ Conservative Dentistry and Periodontology, Postgraduate CoursePeriodontology, Bernhard Gottlieb University Clinic of Dentistry, MedicalUniversity of Vienna, Vienna, Austria. doi: 10.1902/jop.2014.140202

KEY WORDS

Aggressive periodontitis; alveolar bone; dentalcementum; developmental biology; diagnosis;periodontal diseases.

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atrophy.’’6 Ruling out neoplasms, he considered thechanges he described as dystrophic in nature be-cause the inflammation he observed was minimal.He made a point of differentiating marginal atrophyfrom diffuse atrophy.6 Marginal atrophy, he stated,consisted of inflammation of the marginal gingiva(gingivitis).7 In contrast, diffuse alveolar atrophy tookplace in the attachment apparatus. Because minimalinflammation was seen in either the gingiva or theattachment apparatus, he classified the disease asdystrophic.4,6,7 Gottlieb believed that diffuse alveolaratrophy involved systemic metabolic factors, whichmight be responsible for both resorption of the hardstructures and the epithelial proliferation associatedwith deepening of the gingival crevice.6,8,9 In addi-tion, he pointed out that this ‘‘new’’ disease hada distinct clinical presentation, occurred primarily inincisors and molars, and had a comparatively rapidprogression with minimal decay.6,8

Gottlieb stated that tooth migration was frequentlyobserved, especially in the maxillary anterior region.He reported that the pathologic migration he ob-served occurred even when practically no in-flammation was seen in the surrounding gingivaltissues. Chronic inflammation in the region of thecrevice, he believed, was secondary to functionalchanges.6,8 Overall, his underlying hypothesis re-lated to the concept that function is determined byform. One can also surmise that because of thenominal irritating factors seen in the histologicsections examined, he minimalized the contributionof bacteria to this process.6

THE SETTING

At the time Gottlieb described diffuse alveolar atrophy(1920s), Edward Jenner had already demonstratedthat vaccination could prevent smallpox (1796),epidemiology fathered by Dr. John Snow in 1858 wasused to study stillbirths and hospital infections, andLouis Pasteur and Robert Koch had established thegerm theory of disease.10,11 This research related toinfectious diseases was conducted in Europe and waswell known to the research community. With respectto dental research, Kritchevsky and Sequin, two Frenchresearchers working with Pasteur in 1918, addressedissues related to the bacterial initiation of pyorrheaalveolaris and its treatment.12 They went so far as toimplicate these diseases as instigators of systemicinfections and recommended both local and sys-temic treatments to rid patients of spirochetes.12

However, Gottlieb’s biopsies derived from youngerindividuals showed ‘‘minimal irritants’’ and minimalinflammation compared with adult periodontal dis-ease, and so the link between his disease and thegarden-variety diseases studied by other researcherswas not obvious.6,8 As a result, Gottlieb’s disease

was clearly distinguishable from the bacteria-ladenform of chronic periodontitis he described as ‘‘schmutzpyorrhea.’’13

THE INTERPRETATION: BONE REMODELINGAND BARRIER EFFECT

Based on his visual inspection of the cross-sectionalmaterial available, Gottlieb toyed with the idea thatcementum could be the key functional element indiffuse alveolar atrophy.9,14 In 1942, two of his for-mer students, Orban and Weinmann, expanded onGottlieb’s original description and renamed thedisease ‘‘periodontosis’’ (dystrophy = osis; inflam-matory = itis).15 They described the disease in athree-step process. Step one involved the degen-eration of periodontal membrane collagen fibers,causing diminished cementum stimulation and for-mation. In the second stage, they proposed a rapidapical migration of the epithelial attachment alongthe degenerated cementum. The final stage resultedin deepened pocket formation, which provideda home for increased irritants, which led toa heightened local inflammatory response. Theyspeculated that a lack of fiber function resulted ina weakened barrier effect that disrupted alveolarbone remodeling.15

Bone RemodelingGottlieb claimed that, ‘‘we do not need irritation tomake alveolar bone disappear. . .’’ but ‘‘. . .we needstimulation in order to make it form. . ..’’8 In thisembryonic stage of the understanding of periodontaldisease in 1946, Gottlieb was espousing a theory thatbone loss resulted from an imbalance between bonedeposition and bone resorption.8 He was inclined tobelieve that cells of cemental origin were the sourceof alveolar bone stimulation, implying that lack ofcontinuous cementoid deposition was responsiblefor lack of stability of the attachment apparatus anddiminished stimulation of bone cells. Thus, bone losscould be caused by some constitutionally derivedcemental defect that was developmental, systemic,or genetic in nature.8 In the end, in spite of his‘‘cementopathia’’ hypothesis, he decided to leave theresolution of this point open for further discussion.There have been a number of papers describingcemental anomalies, most notably by Page and Baab(1985), and their association with aggressive peri-odontitis.16 Several studies have supported this re-lationship.17-20 An extension of this hypothesis byothers led to the conclusion that bone loss couldoccur without the formation of pockets.21 The ce-mentopathia hypothesis implied that only after ce-mentum degeneration took place would bone loss anda true pocket form. The primary message here, even inits primitive form, was that cells talk to each other.

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Barrier EffectThe barrier effect, according to Gottlieb in his 1946publication, was due to cementum. He proposed thatfiber stability was caused by continuous cementumdeposition.8 Barrier dysfunction, he claimed, was dueto a lack of continuous cementum deposition lead-ing to cementum degeneration. Further, cementumdegeneration would cause disorientation of the inser-tion of the fibers in the attachment apparatus, whichwould lead to apical migration of the epithelial at-tachment and pocket formation. Concomitantly, theresulting lack of alveolar bone stimulation wouldlead to alveolar bone resorption.8 Based on thelack of irritants, bacteria were omitted from consid-eration. In summary, Gottlieb implied that a uniformlayer of cementoid was necessary to ensure that thecontinuity of an intact ligamentous barrier couldprevent epithelial downgrowth.

The authors of this commentary propose that theconcepts of bone resorption coupled with bone de-position and a barrier effect were novel ideas for theirtime and should be reexamined in light of today’sknowledge base.

THE MODERN ERA AND PERIODONTOSIS

Microbial and Immunologic EnlightenmentIn 1965, Loe et al. demonstrated that accumulatingbacteria in the form of dental plaque initiated gingi-vitis, and removal of plaque reversed this inflam-mation.22 Shortly after Loe et al.’s descriptions, therewas an effort to demonstrate that specific microbeswere related to specific forms of periodontal disease.23

In 1976, there was an almost simultaneous dis-covery of an unnamed bacteria that was foundconsistently in the pockets of individuals with peri-odontosis.24,25 The organism proved to be Actino-bacillus actinomycetemcomitans (now known asAggregatibacter actinomycetemcomitans), originallyidentified by Klinger (1912).26 Shortly after 1976,A. actinomycetemcomitans was shown to producea leukotoxin that interfered with the mobility ofpolymorphonuclear leukocytes (PMNs) and phago-cytic activity.27 In the 1980s, a PMN defect wasidentified that was thought to impute an increase inhost susceptibility.28

Then, in 1991, Loe and Brown provided conclusiveevidence of the prevalence of the disease and itsdistribution in adolescents of African and Hispanicdescent.29 It was clear that periodontosis or juvenileperiodontitis (now known as localized aggressiveperiodontitis [LAgP]) was an aggressive disease thatinvolved both microbial and host interactions.30-33

There was still lingering confusion about the role ofcementum and systemic effects on the diseaseprocess.5 However, although Gottlieb’s proposedetiology and their pathogenic consequences were still

open to debate, his original discovery of diffuse alveolaratrophy was now universally recognized as an entity.34

In spite of this recognition, the relationship of his dis-covery to the disease now under scrutiny becameless obvious.35,36

Reinterpretation of Gottlieb’s ConceptsThe disease. Gottlieb’s original report was based onmaterial obtained from soldiers who died in WorldWar I.2 As was the case in World War II, more soldiersdied from infectious diseases than from bullets,perhaps explaining the high number of Gottlieb’spatients with influenza. At that time, little was knownabout the derivation of influenza or how it may haveaffected the tissue examined. To reiterate, diffusealveolar atrophy appeared to be unrelated to localirritants, and microbiology as a science was in itsembryonic stages.6 It is the current authors’ opinionthat Gottlieb’s discovery was based on a conditionwhose etiology may have differed from the LAgP thatone sees today in adolescents of African descent.29

This conclusion is based on: 1) the derivation ofGottlieb’s original samples (whites from Europe); 2)the time of his discovery (microbiology was in itsinfancy); and 3) the lack of irritants observed mi-croscopically (Gottlieb’s approach) that were unlikethe pattern of disease observed by other investigators,which showed massive quantities of irritants seen inchronic periodontitis.12

It is clear by virtue of the number of systemic con-ditions that show a clinical similarity to ‘‘periodontosis’’that further clarification of the systemic and geneticimpact on this disease is needed. Therefore, the currentauthors feel it is worth reexamining Gottlieb’s theoriesin the context of modern times.14,28-32

Bone remodeling in the modern era. Today, whenconsidering bone remodeling, one thinks of osteo-clasts and osteoblasts, a network of chemokines andcytokines that stimulate cells to create or removebone.37 One thinks of receptor activator of nuclearfactor-kappa B (RANK), which reacts with its ligand(RANKL) on the surface of osteoblasts and T-cells.38

One thinks of the fact that osteoclastic activity istriggered by the interaction of osteoblast surface-bound RANKL with the osteoclast precursor cell-bound RANK. A further explanation of this processof bone remodeling indicates that osteoprotegerincan act as a decoy molecule to intercept this RANK/RANKL interaction to reduce and regulate osteo-clastic activity.38 Further, it is now clear that mac-rophage inflammatory protein-1a can act as anupstream stimulator of osteoclastic activity and, insynergy with interleukin (IL)-1b, can further enhancethat activity.39 One also thinks of bone morphogenicproteins (BMPs), BMP-2 and BMP-7, that appear toact as stimulators of bone growth.40 However, the

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general concept of a balance between bone re-sorption and deposition as proposed by Gottlieb withrespect to periodontal disease still stands.

The barrier effect in the molecular era. Today,when considering the barrier effect, one does notnecessarily think of cementoid, fibroblasts, and al-veolar bone; rather, one thinks of cells and moleculesthat contribute to a protective epithelial barrier thatkeeps noxious agents away from vital tissues andorgans. One thinks of epithelial-derived defensinsdesigned to kill or reduce the growth of mucosal ir-ritants.41 One thinks of Toll-like receptors that rec-ognize patterns on the cell walls of bacteria that signalto cytokine networks designed to maintain homeo-stasis by attracting molecules and cells to modulateinfection.42 One thinks of cytokines and chemokinesthat attract PMNs, macrophages, and lymphocytes tothe scene of attack to form a cell barrier (poly wall) toovercome infection.43

Reinterpreting Bone Remodeling and the BarrierEffectDuring the last several years, studies of geneticallymodified rodents have shown how a compromisedbarrier can lead to pocketing in the presence ofminimal irritants and minimal inflammation.44,45

For example, in a dentin matrix acidic phospho-protein 1 (DMP1)-null mouse model of periodontaldisease, genetically defective mice show impropermineralization of bone and dentin that appear asa Rickets-like hypophosphatemic disease.44 Whenthe DMP1-null mouse is compared to its wild type,the following is seen: 1) a disorganized fiber-arrangedattachment apparatus; 2) a significant alteration ofacellular cementum; and 3) subsequent downgrowthof epithelium showing pockets on a histologic level.44

In another rodent model of periodontal disease, de-fects in acellular cementum and periodontal attach-ment fibers are seen in genetically defective bonesialoprotein (BSP)-null mice.45 Thus, the null mouseshows an increase in RANKL and a concomitant in-crease in levels of osteoclasts. The BSP-null mousealso features defects in the cementum–periodontalligament (PDL) interface, PDL disorganization, andepithelial cell downgrowth.45 Both rodent modelsshowed increased bone resorption in the absence ofa significant inflammatory response. Other geneticallyrelated diseases show similar outcomes.46

It could be a complete coincidence, but Vienna washard hit by rickets in the same time period thatGottlieb was obtaining his specimens for histologicevaluation.47

DISCUSSION

Professor Bernhard Gottlieb, the leader of the ViennaDental Research Group, made numerous contribu-

tions to the biologic basis of the practice of dentistry.In this review Gottlieb’s classic 1923 paper6 has beenhighlighted, in which he described ‘‘Diffuse Atrophyof the Alveolar Bone,’’ providing the first descriptionof the entity known at various times as periodontosis,juvenile periodontitis, early-onset periodontitis, andaggressive periodontitis.

Initially, finding minimal irritants and minimal in-flammation, Gottlieb implicated systemic factors asthe primary initiators of disease, and then focused hisattention on cementum. He suggested that an intactcementum played a critical role in the host’s ability toresist local irritants (cementopathia). Gottlieb sug-gested that: 1) bone loss was due to an imbalancebetween bone deposition and bone resorption; 2) anintact host defense barrier was created by cementoid,Sharpey fibers, and alveolar bone; and 3) irritantscausing inflammation were secondary to the pock-eting produced by a weakened barrier effect.

Since Gottlieb’s initial description, interest in thisdisease has intensified and significant progress hasbeen made with respect to microbial and host in-teractions related to this entity. His ideas related tobone resorption and deposition and barrier effectshave been forgotten as research has moved from themicroscopic to the molecular level.

So where does the issue stand today? Even as theinfectious nature of aggressive periodontitis becomesbetter understood, the following questions remainunanswered. Why is there a first molar/central incisordistribution? Why the so-called mirror image? Whyis there a lack of correlation between local irritantsand disease? Why is this disease more prominent inadolescents and younger children? Is there a differ-ence in the disease seen in African and Hispanicindividuals compared with Asian and white in-dividuals? Is there more than one disease? It is quitepossible that genetic/systemic influences on de-velopmental biology of the dentition might providethe critical missing links that could help to answerthese and other questions.48,49

The studies that took place in the laboratories ofVienna in the early 1920s were the first of their kind.The meticulous histologic preparations of humanjaws were widely acknowledged as exceptional.These preparations were first shown in the UnitedStates at a Federation Dentaire Internationalemeeting in Philadelphia in 1926.1-3 The Vienna Groupwas disbanded in 1938 with the German annexation ofAustria. The scientists who worked with Dr. Gottliebwent on to take positions at various universities in theUnited States.2 Direct contact and interaction ofAmerican and European scholars provided a hugebenefit to academicians and clinicians alike. Theexplosion of information in recent times relative toLAgP can be best exemplified when one searches the

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literature using search terms ‘‘periodontosis’’ or‘‘aggressive periodontitis.’’ Using PubMed as thesearch engine, the authors discovered that 1,275manuscripts have been published from 1999 to2014. By comparing that number to the 75 paperspublished from 1923 to 1948 (a similar 25-yearspan), one can clearly see the renewed interest inthis disease. It is the current authors’ hope thatthis review can serve to credit Gottlieb for his in-itial discovery, put the discovery in context, andstimulate interest in the important questions thatremain unanswered.

CONCLUSIONS

The field of periodontology is greatly indebted toBernhard Gottlieb for his scholarly activity, especiallyfor his discovery of this rapidly progressive form ofperiodontal disease. This article honors Gottlieb’soriginal discovery and the groundbreaking researchit stimulated. The current authors support thepremise that visionary discoveries deserve recog-nition, take time to be fully understood, and oftenraise more questions than answers. With that said,the authors are profoundly grateful to this excep-tional scholar (Fig. 1). It is noteworthy that theMedical University of Vienna has named its ViennaDental School ‘‘The Bernhard Gottlieb UniversityClinic of Dentistry.’’

ACKNOWLEDGMENTS

Dr. Bruckmann is a senior staff member at BernhardGottlieb University Clinic of Dentistry. Drs. Fine,Cohen, and Bimstein report no conflicts of interestrelated to this commentary.

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34. Armitage GC. Development of a classification systemfor periodontal diseases and conditions. Ann Periodon-tol 1999;4:1-6.

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37. Han X, Kawai T, Taubman MA. Interference withimmune-cell-mediated bone resorption in periodontaldisease. Periodontol 2000 2007;45:76-94.

38. Nagasawa T, Kiji M, Yashiro R, et al. Roles of receptoractivator of nuclear factor-kappaB ligand (RANKL) andosteoprotegerin in periodontal health and disease. Peri-odontol 2000 2007;43:65-84.

39. Al-SabbaghM, AlladahA, Lin Y, et al. Bone remodeling-associated salivary biomarker MIP-1a distinguishesperiodontal disease from health. J Periodontal Res2012;47:389-395.

40. KnippenbergM,HelderMN,ZandiehDoulabiB,WuismanPI, Klein-Nulend J. Osteogenesis versus chondrogenesisby BMP-2 and BMP-7 in adipose stem cells. BiochemBiophys Res Commun 2006;342:902-908.

41. Cutler CW, Teng Y-T. Oral mucosal dendritic cells andperiodontitis: Many sides of the same coin with newtwists. Periodontol 2000 2007;45:35-50.

42. Kinane DF, Demuth DR, Gorr S-U, Hajishengallis GN,Martin MH. Human variability in innate immunity.Periodontol 2000 2007;45:14-34.

43. Fine DH, Kaplan JB, Kachlany SC, Schreiner HC. Howwe got attached to Actinobacillus actinomycetemco-mitans: A model for infectious diseases. Periodontol2000 2006;42:114-157.

44. Ye L, Zhang S, KeH,Bonewald LF, Feng JQ. Periodontalbreakdown in the Dmp1 null mouse model of hypo-phosphatemic rickets. J Dent Res 2008;87:624-629.

45. Foster BL, Soenjaya Y, Nociti FH Jr., et al. Deficiency inacellular cementum and periodontal attachment in bspnull mice. J Dent Res 2013;92:166-172.

46. Foster BL, Ramnitz MS, Gafni RI, et al. Rare bonediseases and their dental, oral, and craniofacial man-ifestations. J Dent Res 2014;93(Suppl. 7):7S-19S.

47. Carpenter KJ. Harriette Chick and the problem ofrickets. J Nutr 2008;138:827-832.

48. Fourel J. Periodontosis, juvenile periodontitis or Got-tlieb syndrome? Report of 4 cases. J Periodontol 1974;45:234-237.

49. Hart TC. Genetic aspects of periodontal disease. In:Bimstein E, Needleman HL, Karimbux N, VanDyke TE,eds. Periodontal and Gingival Health and Diseases.Children, Adolescents and Young Adults. London:Martin Dunitz; 2001:189-204.

Correspondence: Dr. D. Walter Cohen, Drexel UniversityCollege of Medicine, 2900 Queen Lane, Philadelphia, PA19129. E-mail: jmitchel@drexelmed.edu.

Submitted April 6, 2014; accepted for publication July 11,2014.

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