The epidemiological, clinical interventional, and animal model-based studies discussed in the various chapters of this volume collectively indicate that the association of periodontitis and linked co morbidities is quite complex, involving both common risk factors and pathophysiology as well as bidirectional causal relationships (independent of known confounding factors). Despite the enormous progress made in the field,17,34,35,56-63 unequivocal evidence that effective treatment of periodontitis can ameliorate the risk or incidence of epidemiologically-lined co morbidities conditions is not currently available. In this regard, multi-center randomized controlled clinical trials are required to implicate periodontitis as a modifiable risk factor for linked co morbidities.
Further improvement of local periodontal treatment via innovative adjunctive host-modulation approaches, 39,40 such as by modulating complement with the C3-targeted drug AMY-101, which showed efficacy in a recent phase 2a trial in patients with periodontal inflammation, may greatly contribute to prevent systemic inflammation and pro-mote overall health.Achieving a holistic and mechanistic understanding of periodontitis-associated co morbidities may lead to new therapeutic options for the treatment of periodontitis and associated co morbidities. Some of these novel approaches may be ‘central’ rather than ”local,” for instance the targeting of maladaptive training of hematopoietic progenitors in the bone marrow as a central hub link-ing distinct co morbidities. It is therefore important to accelerate the transfer of research findings from basic and clinical studies into routine clinical practice.