Systematic review of ratios between disease /health periodontitis modulators and meta-analysis of their levels in gingival tissue and biological fluids

Authors were assigned the task to develop case definitions for periodontitis in the context of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. The aim of this manuscript is to review evidence and rationale for a revision of the current classification, to provide a framework for case definition that fully implicates state-of-the-art knowledge and can be adapted as new evidence emerges, and to suggest a case definition system that can be implemented in clinical practice, research and epidemiologic surveillance.

The discovery of the RANKL/RANK/OPG system in the mid 1990s for the regulation of bone resorption has led to major advances in our understanding of how bone modeling and remodeling are regulated. It had been known for many years before this discovery that osteoblastic stromal cells regulated osteoclast formation, but it had not been anticipated that they would do this through expression of members of the TNF superfamily: receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG), or that these cytokines and signaling through receptor activator of NF-kappaB (RANK) would have extensive functions beyond regulation of bone remodeling. RANKL/RANK signaling regulates osteoclast formation, activation and survival in normal bone modeling and remodeling and in a variety of pathologic conditions characterized by increased bone turnover. OPG protects bone from excessive resorption by binding to RANKL and preventing it from binding to RANK. Thus, the relative concentration of RANKL and OPG in bone is a major determinant of bone mass and strength. Here, we review our current understanding of the role of the RANKL/RANK/OPG system in bone modeling and remodeling.

Classification systems are necessary in order to provide a framework in which to scientifically study the etiology, pathogenesis, and treatment of diseases in an orderly fashion. In addition, such systems give clinicians a way to organize the health care needs of their patients. The last time scientists and clinicians in the field of periodontology and related areas agreed upon a classification system for periodontal diseases was in 1989 at the World Workshop in Clinical Periodontics. Subsequently, a simpler classification was agreed upon at the 1st European Workshop in Periodontology. These classification systems have been widely used by clinicians and research scientists throughout the world. Unfortunately, the 1989 classification had many shortcomings including: 1) considerable overlap in disease categories, 2) absence of a gingival disease component, 3) inappropriate emphasis on age of onset of disease and rates of progression, and 4) inadequate or unclear classification criteria. The 1993 European classification lacked the detail necessary for adequate characterization of the broad spectrum of periodontal diseases encountered in clinical practice. The need for a revised classification system for periodontal diseases was emphasized during the 1996 World Workshop in Periodontics. In 1997 the American Academy of Periodontology responded to this need and formed a committee to plan and organize an international workshop to revise the classification system for periodontal diseases. The proceedings in this volume are the result of this reclassification effort. The process involved development by the Organizing Committee of an outline for a new classification and identification of individuals to write state-of-the-science reviews for each of the items on the outline. The reviewers were encouraged to depart from the preliminary outline if there were data to support any modifications. On October 30-November 2, 1999, the International Workshop for a Classification of Periodontal Diseases and Conditions was held and a new classification was agreed upon (Fig. 1). This paper summarizes how the new classification for periodontal diseases and conditions presented in this volume differs from the classification system developed at the 1989 World Workshop in Clinical Periodontics. In addition, an analysis of the rationale is provided for each of the modifications and changes.