Activation of osteoclasts by food allergies
Periodontitis is a recurring topic in dentistry. Despite major medical advances, we have not yet succeeded in curbing this widespread disease. What we have succeeded in doing quite well with caries reduction does not apply to inflammation of the periodontium. The German Oral Health Study, a survey commissioned by the German Dental Association and the National Association of Statutory Health Insurance Dentists, looks at the oral health of Germans at regular intervals. Although the situation has improved overall, there is still a need for further action. The proportion of adults with periodontal disease is still too high at 51-64%. Demographic trends can only explain this development to a limited extent.
Since the pioneering work of prophylaxis pioneers Axelsson and Lindhe in the 1970s, there is no longer any doubt that bacterial plaque (plaque/biofilm) is involved in the development of periodontitis. Dental calculus and resulting concretions on the root surface serve as "slides" for germs into the depths of the periodontium.Despite all efforts to reduce germs, however, it is also evident that bone loss and deep pockets can form even without germ colonization. Apparently, there are also other mechanisms that induce bone resorption.
There is general agreement among periodontists that infection of the gingival pockets initiates an immune cascade, in the course of which activation of osteoclasts by cytokines and bone resorption may occur. However, it must also be taken into account that more tolerance-inducing regulatory T cells are found within the oral mucosa than elsewhere in the body. Reactions of the immune system, especially in the area of T cell/macrophage reactions are always systemically effective, therefore it is also conceivable that immune reactions from other locations in the body have an impact on bone metabolism of the oral system.
This is more obvious than to deal with the intestine, because here lies about 80% of our immune function. Already in TCM it is taught that intestine and mouth behave like mirror images of each other. However, this knowledge arose without the pathophysiological background of this relationship being clear.
The intestinal mucosa (GALT - Gut associated lymphoid tissue) is a complex system. It represents the transition between inside and outside, because here the body controls very precisely what is allowed to pass the interface. To protect against anything coming from the outside, the epithelial cells of the mucosa are very tightly linked together. This linkage occurs through the tight junctions. These are narrow bands of membrane proteins that connect the epithelial cells of the intestinal mucosa to each other (Fig. 1). They close the intercellular space and thus form a diffusion barrier. This controls the flow of dissolved amino acids, sugars and fatty acids, but also of food proteins.
Numerous substances are involved in the pathophysiological regulation of the tight junctions: secretory IgA, enzymes, neuropeptides, neurotransmitters, peptides from food, lectins, yeasts, aerobic and anaerobic bacteria, parasites, proinflammatory cytokines, free radicals and a dysfunction of regulatory T cells.
The macrophages, which as antigen-presenting cells form the beginning of the specific immune defense, are positioned very close to the epithelial cells and pierce the intercellular junctions with long projections to search for potential antigens in the intestinal lumen to present them to the T cells.
In order to illustrate the effect of the immune system on bone metabolism, one must primarily consider the interaction of macrophages (or dentritic cells, as they are called when they are stationed in the tissue) and lymphocytes. The task of macrophages is to offer antigenic material to T lymphocytes patrolling in the blood by taking it up and presenting its fragments on the cell surface.
T-lymphocytes have about 109 receptors of different spatial structure on their surface to be able to react to a variety of allergens. If the presented allergen docks at the receptor of the T-cell, this results in an activation of the T-cell in the sense of type IV allergy and a whole series of cytokines are released, which unfold a wide variety of effects. These cytokines control a variety of physiological processes.
A central role is played by the macrophage cytokines TNF-alpha and IL1, as these have a major effect on the body, including the activation of osteoclasts, which promote bone resorption (Fig. 2).
There is a wide range of evidence in the literature about the effect of TNF-alpha. As early as 2001, Zhang et al. pointed to the association of TNF-alpha with osteoclast activity. Various other studies were able to repeat this evidence. For example, the importance of TNF-alpha and chronic periodontitis was also pointed out in 2008 by Schulz et al.
The link between TNF-alpha, gut health and bone loss was provided by Iqbal et. al in 2016 with their experiments with germ-free mice. The link to nutrition was made as early as 2013 with the work of Ambroszkiewicz. There, it was demonstrated that TNF-alpha/RANKL-dependent bone resorption processes are accelerated in subjects with cow's milk allergy.
These processes take place slowly starting in the sense of a "silent inflammation". This means that they run below an acute threshold and are not necessarily noticed by the patient. Sometimes it takes years before symptoms appear. With regard to the processes in the intestine, this means that at the beginning the reactions are still moderate, but the TNF-alpha slowly causes the tight junction in the intestine to dissolve. At the beginning the damage is still limited, but as the allergic reaction to one or more foods progresses, the boundary layer of the intestinal epithelium begins to dissolve and we get a so-called leaky gut syndrome, i.e. a permeable intestine. This can be detected in the laboratory by the appearance of zonulin in the blood.
At the same time, a change takes place in the bone of the alveolar process, where activated osteoclasts promote bone resorption. This, together with the additional bacterial colonization and the reaction to it, can lead to permanent bone loss. Food intolerances manifest themselves mainly in horizontal bone loss.
In this process, the genetics of inflammation plays an additional decisive role. The reading for the production of the inflammatory cytokines takes place at different gene loci, where it is determined how much of the cytokines TNF-alpha, IL1 or also the inhibitory cytokine TNF-alpha receptor antagonist is produced in response to a corresponding stimulus. A harmonious interaction is crucial for a regulated immune response and is a real balancing act for the immune system.
The inflammatory genetics are represented in the grades 0 - 4. 0 = Low-Responder, 4 = High-Responder and the intermediate grades. All food-induced bone resorption processes are found in grades 2 - 4. Thus, inflammatory genetics can be considered a marker for periodontitis risk.
The diagnosis of type IV food intolerances is made via the lymphocyte transformation test (LTT). The IgG tests for foods are only suitable to a limited extent for this purpose. Although they can help to shed additional light on the background of a leaky gut syndrome, they cannot explain TNF-alpha activation, which is important for explaining periodontitis. In our practice, this is done by the LTT "Top 25 Foods" from IMD Berlin, where the 25 most frequently tested foods are recorded. The inflammatory genetics can also be recorded there (Figs. 3 and 4).
It is important to differentiate food-induced bone resorption from a lack of mucosal immunity. Bone resorption processes occur in patients with inflammation grade 0 - 1, but then there is usually a deficit in the primary defense against germs in the mucosa. This should then be additionally clarified. The secretory IgA, the mannose-binding lectin MBL and the phagocytosis capacity of the granulocytes are examined.
Of course, therapy is carried out strictly according to the rules of periodontology, i.e. curettage, calculus removal and root planing as well as reduction of granulation tissue. In parallel, however, a reduction or avoidance of food triggers should be aimed for and, if possible, maintained in the future. Long-term maintenance of the health of the periodontal tissues is thus ensured.
The detection of food allergies is proving to be an effective pillar in periodontitis therapy. Foods can lead to the release of TNF-alpha and IL1 via a macrophage T-cell reaction in the mucosa (Peyer`s plaques), which cause osteoclast activation. These are systemic in nature, but are most likely to be seen in the jawbone.
Together with increased inflammatory genetics in terms of an inflammatory highresponder, bone resorption may be even more pronounced.
Tracking down the food triggers and appropriate food restriction then represents an additional therapeutic option.
A consideration of the intestinal function and its allergic potency is therefore part of a holistic view of periodontitis.
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