Systemic and chronic inflammatory diseases have been on the rise in the 21st century, while also being an increasingly discussed topic in the medical field. Today, we are aware that the oral cavity plays an important role in diagnosing and treating these diseases, with a good dental diagnosis and great oral health being essential to successfully treat them. The presence of periodontal disease is one of the most talked about topics when it comes to systemic diseases, but we cannot forget that periodontitis is not the only oral disease associated with general health problems. There are others, such as jawbone cavitations, which can influence our systemic health.
The role of bone marrow
Bone marrow is composed of different areas with various cellular functions. On the one hand, mesenchymal cell systems are a source of osteoblasts, fibroblasts and fat cells; on the other hand, the hematopoietic system fills in the spaces of the bone marrow stroma and exerts significant influence on the immune system. When it comes to the jawbone, the long-term success of any oral surgery depends on the interactions between these two cell systems, which significantly control the regenerative process and are essential components of bone metabolism. Both osteoclasts and osteoblasts are determinant to bone mass, as well as to the bones’ structure and resistance, by way of their respective functions regarding resorption and bone formation.
Bone remodelling is a spatially coordinated process that occurs throughout our life, wherein the older bone is removed by osteoclasts and replaced by bone forming osteoblasts. Filling cavities which are formed due to that resorption is an incomplete process in many pathological conditions, resulting in a liquid loss of bone mass in every remodelling cycle. A unique situation of bone remodelling seems to occur in the case of fatty degenerative osteonecrosis in the medullary spaces of the jawbone, also known as FDOJ. It is crucial to understand that during any manipulation of the jawbone – e.g., placement of implants and dental extraction of the third molars – various inflammatory processes are activated, which are followed by the physiological mechanisms of bone healing.
What is FDOJ, exactly?
When chronic inflammation is present, it will strongly influence osteoimmunology, imposing profound metabolic, structural, and functional changes in the bone. The so-called medullary edemas, or circumscribed focal bone defects in the mandible (focal osteoporotic bone marrow defect), are often described and discussed in scientific literature.
These cavitations in the mandible are characterised by necrotic fractions of the bone marrow, and the fatty degenerative osteolysis of the jawbone (FDOJ) can either be painful or remain asymptomatic for years. Areas which are affected by FDOJ can be impacted by the super expression of inflammatory mediators, such as chemokine ligand 5 (CCL5), also known as RANTES (Regulated on Activation, Normal T-cell Expressed and Secreted).
The macroscopic characteristics of the samples from FDOJ bones are consistently similar. Due to the softening of the bone substance, the medullary space can be curetted. The degeneration of the spongy bone spreads to the mandibular region, ultimately reaching the inferior alveolar nerve canal.
A German research group with whom we collaborate has been documenting the seriousness of these injuries in their publications for many years.
Figure 1 is an example of FDOJ. In the CBCT (an essential diagnosis tool to detect the presence of cavitations), we can clearly see a predominantly radiolucent image of the right lower jaw (4th quadrant).
Figure 1
Figures 2 and 3 represent a FDOJ sample exhibiting a predominantly fatty transformation of the upper jaw, as well as the corresponding CBCT, which shows an apparently radiolucent area in the upper jaw (tooth #21).
Figure 2
Figure 3
Specific super expression of RANTES/CCL5 in FDOJ and its possible connection with systemic diseases
The adipose tissue’s inflammatory response associated with a systemic inflammatory response is well known and has been frequently studied. The secretion of inflammatory chemokines mediates the systemic effects of the adipose tissue’s inflammation, and most normal adult tissues contain few, if any, positive RANTES/CCL5 cells. In opposition to this, the expression of RANTES/CCL5 increases significantly in inflamed regions.
These results indicate a higher expression of RANTES/CCL5 than the one present when there was no inflammation, which suggests that several inflammatory actions are occurring at the moment, increasing the expression of this mediator, as it typically occurs with FDOJ.
Reduction in blood flow and capillary density, followed by ischemia in the jawbone’s medullary spaces may lead to hypoxia. These triggers result in the activation of signalling pathways that favour a predisposition to develop chronic diseases. In general, cell communication systems are organised in a cascade with sequenced stages, and the signal messengers, such as cytokines, carry instructions which are received by cells with specific receptors that are capable of recognising them.
In previous publications, this chronic inflammatory process was defined as fatty degenerative osteonecrosis of the jawbone (FDOJ). The clinical material presented here was obtained from patients who were surgically treated for possible chronic inflammation in the mandibular region, in which FDOJ should contribute to systemic inflammatory diseases.
The inability to correctly diagnose this bone marrow disease before or during the insertion of a dental implant may explain why, in some cases, there are dental implants that do not integrate regardless of the fact that the correct protocol was followed by the doctor.
Oral health is important in diagnosing and treating systemic diseases
Pro-inflammatory signalling mediators, and RANTES/CCL5 in particular, affect the organism in a systemic manner and can result in chronic inflammatory processes. It is generally accepted that, in the case of an imbalance between cytokines and their specific inhibitors, there exists a high predisposition to develop chronic inflammatory diseases. In these cases, cytokines band together to initiate an immune response that induces acute inflammatory events until a persistent chronic inflammation is created. This means that, in order to maintain a healthy condition, cytokine-producing mechanisms must be controlled. For that to happen, it is necessary to understand both the origin and the trigger that sets off the production of these cytokines, keeping in mind that this origin may be dental. For that reason, it is important to reinforce that oral health plays a prominent role in the diagnosis and treatment of systemic diseases.
FDOJ represents a new phenomenon of cellular inflammatory response in which cytokines are not triggered by the presence of a bacteria or virus. Thus, this hypothesis suggests that the RANTES/CCL5 signalling is a chronic disorder usually derived from FDOJ areas which can contribute to the development of chronic inflammation.
