perko

At the heart of Biological Dentistry lies the profound recognition that oral health is not an isolated concern but an integral component of overall well-being. This understanding begins with a detailed examination of the microbiome and osteoimmunology, two pillars that underpin the biological mechanisms governing oral health.

The oral cavity houses a thriving ecosystem, hosting a diverse community of microorganisms, including over 700 distinct bacterial species, viruses, and fungi. These inhabitants, along with their metabolites and pro-inflammatory mediators, wield a remarkable capacity to exert influence far beyond their immediate domain. Specific attention is devoted to pathogenic microorganisms such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. These bacteria, recognized for their roles not only in causing localized oral conditions but also in driving systemic implications, illustrate the interconnectedness of oral and systemic health. Porphyromonas gingivalis, for instance, has been closely associated with gut dysbiosis and its potential to disrupt the gut microbiome equilibrium. Additionally, the secretion of gingipain by this bacterium has been implicated in the progression of Alzheimer’s disease. Likewise, Aggregatibacter actinomycetemcomitans is examined for its potential to heighten the metastatic potential of pancreatic cancer, thereby highlighting the systemic consequences of oral health. Crucially, the influence of these bacteria often manifests through inflammatory responses, reinforcing the central role of inflammation in both local and systemic pathologies.

Osteoimmunology, a burgeoning field investigating the intricate interaction between the immune system and bone metabolism, assumes critical importance in comprehending the complex relationship between inflammation and bone health. A paradigm shift from viewing bones as static structures to dynamic, continuously remodeling tissues is articulated. The regulatory mechanisms governing this remodeling process, notably RANKL (receptor activator of nuclear factor kappa B ligand) and OPG (osteoprotegerin), which modulate the activity of osteoclasts, are elucidated. Particular emphasis is placed on the influence of bacterial lipopolysaccharides, with Porphyromonas gingivalis as a notable example. These lipopolysaccharides have been shown to upregulate RANKL expression in osteoblasts, ultimately leading to bone loss in periodontal disease.

This exploration underscores the critical need to recognize the intricate connections between oral health, the microbiome, osteoimmunology, and systemic well-being. Such recognition not only underscores the need for a comprehensive approach but also aligns with the evolving paradigm of modern healthcare, which increasingly focuses on healthspan over lifespan. Today’s healthcare system recognizes that longevity alone does not equate to quality of life. Instead, the emphasis is shifting towards enhancing healthspan – the period of life marked by good health and well-being. In this context, Biological Dentistry takes on a pivotal role, as it acknowledges that oral health is an integral element of overall healthspan.

In conclusion, this comprehensive exploration underscores the vital importance of Biological Dentistry within the evolving landscape of modern healthcare. It serves as a compelling argument for healthcare systems to prioritize healthspan, promoting both oral and overall health through a deeper understanding of the connections between oral health, the microbiome, osteoimmunology, and systemic well-being. This paradigm shift represents a crucial step towards enhancing the quality of life for individuals across the lifespan.

This abstract delves into the indispensable role of the microbiome and osteoimmunology as pivotal elements influencing ove rall systemic health within the domain of dentistry. Within the oral cavity resides a myriad of diverse bacteria, viruses, and fungi, comprising a staggering 700 distinct species. These microorganisms, together with their byproducts and inflammatory mediat ors, have the potential to traverse various pathways, including ingestion via saliva, thereby potentially exerting an impact on other bodily regions.

Research studies have illuminated the significance of specific bacteria, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, not only in causing localized oral ailments but also in bearing systemic ramifications. Porphyromonas gingivalis has been associated with gut dysbiosis, as it manages to withstand the harshness of stomach acid an d disrupts the equilibrium of the gut microbiome. Additionally, the gingipain secreted by this bacterium has been implicated in the progression of Alzheimer’s disease. Conversely, Aggregatibacter actinomycetemcomitans has been discovered to heighten the me tastatic potential of pancreatic cancer. Rather than directly causing destruction, the inflammatory response triggered by these bacteria contributes to the deterioration of tooth supporting tissues and aggravates systemic inflammation.

Osteoimmunology, th e field that studies the interaction between the immune system and bone metabolism, offers valuable insights into the intricate relationship between inflammation and bone health. Previously viewed as relatively inert, bone is now recognized as a dynamic ti ssue undergoing constant remodeling. This process is governed by diverse factors, including RANKL (receptor activator of nuclear factor kappa B ligand) and OPG (osteoprotegerin), which regulate osteoclast activity. Bacterial lipopolysaccharides, such as th ose emanating from Porphyromonas gingivalis, have been demonstrated to enhance RANKL expression in osteoblasts, leading to bone loss in periodontal disease.

Appreciating these complex connections between oral health, the microbiome, osteoimmunology, and s ystemic health is of paramount significance within the realm of biological dentistry. By acknowledging the influence of oral pathogens and inflammation on systemic well being, a comprehensive approach can be embraced to foster both oral and overall health.

In the pursuit of enhancing osseointegration and implant stability, a pilot study was conducted utilizing a unique Ion Induction Therapy (IIT) protocol, along with IV Ozone. Preliminary results showcased remarkable outcomes, with Osstell ISQ scores avera ging 72 after 16 weeks post op. This data presents a notable advantage over a comparable study by Vladimir Kokovic et al., which achieved an average ISQ value of 64 for the same type of implant. Notably, ISQ scores above 70 indicate high stability, 60 69 s ignify medium stability, and scores below 60 denote low stability. This promising integration of IIT and IV Ozone highlights the potential to elevate osseointegration, thereby underlining the practical impact of these interventions in the realm of biologic al dentistry.

Further exploration through research endeavors and clinical investigations is warranted to advance our comprehension and devise effective strategies in biological dentistry, ultimately enhancing patient outcomes and systemic well being.

Author:
Dr. med. dent. Sebastjan Perko, Phd.
dr.perko@maha.si www.maha.si

References:
• Abou-Khalil, R., Yang, F., & Lieu, S. (2013). Regulation of osteogenesis and bone remodeling by hedgehog signaling. Connective Tissue Research, 54(5), 373-378.
• Alvarez, C., Monasterio, G., Cavalla, F., Córdova, L. A., Hernández, M., Heymann, D., Garlet, G. P., Sorsa, T., Pärnänen, P., Lee, H. M., Golub, L. M., Vernal, R., & Kantarci, A. (2019). Osteoimmunology of Oral and Maxillofacial Diseases: Translational Applications Based on Biological Mechanisms. Frontiers in Immunology
• Boyce, B. F., & Xing, L. (2008). Biology of RANK, RANKL, and osteoprotegerin. Arthritis Research & Therapy, 9(Suppl 1), S1.
• Chow, S. K. H., Leung, K. S., & Qin, J. (2019). Treatment of osteoporosis with electric and electromagnetic fields. Journal of Osteoporosis, 2019, 7539162.
• Ciancaglini, R., Radaelli, G., & Pagani, S. (1999). Association of temporomandibular disorder symptoms with anxiety and depression in the general Italian population. Journal of Oral Rehabilitation, 26(1), 52-59.
• Grgič, V., Karba, R., & Brilej, D. (2019). Pulsed electromagnetic field therapy in the treatment of pain and other symptoms in fibromyalgia: A randomized controlled study. Bioelectromagnetics, 40(5), 351-360.
• Guo, Q., Wang, Y., Xu, D., Nossent, J., Pavlos, N. J., Xu, J., & Zheng, M. H. (2015). Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Research, 3, 15022.
• Hak, D. J., & Fitzsimmons, R. J. (2017). Orthopedic implications for osteoporosis. In Osteoporosis in Orthopedics (pp. 13-18). Springer, Cham.
• Ju, C., & Tacke, F. (2016). Hepatic macrophages in homeostasis and liver diseases: from pathogenesis to novel therapeutic strategies. Cellular and Molecular Immunology, 13(3), 316- 327.
• Kokovic, V., Rahman, M., Rahman, B., & Tattan, M. (2015). Assessment of Implant Stability of Two-piece Zirconium Dioxide Implants using Resonance Frequency Analysis: A Pilot Study.
• Lacey, D. L., Timms, E., Tan, H. L., Kelley, M. J., Dunstan, C. R., Burgess, T., … & Kostenuik, P. J. (1998). Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and
activation. Cell, 93(2), 165-176.
• Manolagas, S. C. (2010). From estrogen-centric to aging and oxidative stress: A revised
perspective of the pathogenesis of osteoporosis. Endocrine Reviews, 31(3), 266-300.
• Papageorgiou, S. N., Papadopoulos, M. A., & Katsarou, Z. (2008). Osteoimmunology: The role of the immune system in bone metabolism and disease. Critical ReviewsTM in Immunology,
28(3), 239-262.
• Pufe, T., Lemke, A., Kurz, B., Petersen, W., & Tillmann, B. (2001). Mechanical overload
induces VEGF in cartilage discs via hypoxia-inducible factor. American Journal of Pathology,
158(1), 185-192.
• Rauner, M., & Hofbauer, L. C. (2007). Mode of action of bisphosphonates: Nitrogen-containing
bisphosphonates induce osteoblast apoptosis in vitro. Bone, 40(3), 904-910.
• Ritz, U., Gerke, V., & Vincenz, C. (2012). Osteopontin functionally activates solid tumor cell growth, intratumoral macrophages, and vascular cells: A novel pathway potentially involved in
osteosarcoma tumor progression. Cancer Research, 72(1), 146-156.

• Rossini, M., Adami, G., Adami, S., Viapiana, O., & Gatti, D. (2018). Safety and efficacy of tibolone in postmenopausal women: A comprehensive review. Expert Opinion on Drug Safety, 17(8), 787-796.
• Rucci, N., & Teti, A. (2010). Osteomimicry: How tumor cells try to deceive the bone. Frontiers in Bioscience (Scholar Edition), 2, 907-915.
• Suda, T., Takahashi, N., & Udagawa, N. (1999). Acidic microenvironment and bone resorption. In Seminars in Immunology (Vol. 11, No. 3, pp. 175-183). Academic Press.
• Szentpétery, A., & Hofbauer, L. C. (2015). Highlights in bone and cartilage research: Update 2015. Immune-bone interactions. Osteoporosis International, 26(3), 677-682.
• Tan, C., Liu, Y., Li, W., & Li, D. (2017). Osteoblast: Functions, differentiation, and bone development. In Stem Cells in Craniofacial Development and Regeneration (pp. 1-36). Springer, Cham.
• Tanaka, Y., Tanaka, R., Miyake, Y., Kanazawa, I., Tanaka, K., Sunaga, M., … & Yamaguchi, T. (2016). Ibandronate suppresses osteoclastic and osteoblastic changes in the bone marrow of rheumatoid arthritis model mice treated with prednisolone. Arthritis Research & Therapy, 18(1), 1-12.
• Wang, L., Wang, Y., Han, Y., & Zhang, G. (2015). Osteoblast-derived PGE2 promotes pannexin1-mediated MSC osteogenic differentiation via the GSK3β/β-catenin signaling pathway. Journal of Cell Science, 128(22), 4317-4327.
• Yavropoulou, M. P., van Lierop, A. H., & Hamdy, N. A. (2014). Osteoimmunology: The hidden immune regulation of bone metabolism. Endocrine Reviews, 35(3), 458-488.
• Zhang, J., Tanaka, H., Chigusa, M., Nagata, K., & Kawamura, Y. (2018). Quantitative analysis of multi-mechanistic effects of extremely low frequency magnetic fields on gene expression levels in human dermal fibroblasts. Journal of Radiation Research, 59(3), 325-336.

The oral cavity harbors a diverse array of bacteria, viruses, and fungi, with over 700 different species residing in the mouth. These microorganisms, along with their byproducts and inflammatory mediators, can travel through pathways such as saliva ingestion, potentially impacting other parts of the body.

Studies have revealed that certain bacteria, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, not only cause localized oral diseases but can also have systemic implications. Porphyromonas gingivalis has been linked to gut dysbiosis, surviving stomach acid and disrupting the gut microbiome. Moreover, gingipain secreted by this bacterium has been implicated in the development of Alzheimer’s disease. Aggregatibacter actinomycetemcomitans, on the other hand, has been found to increase the metastatic potential of pancreatic cancer. The inflammatory response triggered by these bacteria, rather than their direct destruction, contributes to the breakdown of tooth-bearing tissues and feeds into systemic inflammation.

Osteoimmunology, the study of the interaction between the immune system and bone metabolism, provides insights into the complex relationship between inflammation and bone health. Bone, once considered relatively inert, is now recognized as a dynamic tissue undergoing constant remodeling. This process is regulated by various factors, including RANKL (receptor activator of nuclear factor kappa B ligand) and OPG (osteoprotegerin), which modulate osteoclast activity. Bacterial lipopolysaccharides, such as those from Porphyromonas gingivalis, have been shown to increase RANKL expression in osteoblasts, resulting in bone loss in periodontal disease.

Understanding these intricate connections between oral health, the microbiome, osteoimmunology, and systemic health is of utmost importance in biological dentistry. By considering the impact of oral pathogens and inflammation on systemic health, a comprehensive approach can be adopted to promote oral and overall well-being. Further research and clinical investigations are warranted to advance our understanding and develop effective strategies in biological dentistry to improve patient outcomes and systemic health.