Categories: Sem categoria

Author

White Clinic

Share

As doenças sistémicas e inflamatórias crónicas têm vindo a aumentar no século XIX, e é um tópico cada vez mais discutido na área da medicina. Hoje em dia, sabemos que a cavidade oral tem um papel importante no diagnóstico e tratamento destas doenças. Um bom diagnóstico dentário e uma boa saúde oral são essenciais para o sucesso do tratamento destas doenças. A presença de doença periodontal é dos temas mais abordados quando falamos de doenças sistémicas, mas não podemos esquecer que a periodontite não é a única doença oral que está associada a problemas de saúde geral. Existem outras, tais como as cavitações ósseas nos maxilares, que podem influenciar a nossa saúde sistémica.

O papel da medula óssea 

A medula óssea é composta por diferentes áreas com funções celulares variadas. Por um lado, os sistemas de células mesenquimais são fontes de osteoblastos, fibroblastos e células de gordura; por outro, o sistema hematopoiético preenche os espaços do estroma medular e exerce uma influência significativa no sistema imunológico. No osso maxilar, o sucesso a longo prazo de qualquer cirurgia oral depende das interações desses dois sistemas celulares diferentes que controlam significativamente o processo de regeneração e são componentes essenciais do metabolismo ósseo. Os osteoclastos e osteoblastos determinam a massa óssea, bem como a estrutura e resistência do osso por meio das suas respetivas funções na reabsorção e formação óssea. A remodelação óssea é um processo espacialmente coordenado ao longo da vida, no qual o osso mais antigo é removido por osteoclastos e substituído por osteoblastos formadores de osso. O preenchimento das cavidades que se formam devido à reabsorção é incompleto em muitas condições patológicas, resultando numa perda líquida de massa óssea durante cada ciclo de remodelação. Uma situação única de remodelação óssea parece ocorrer no caso da osteonecrose degenerativa gordurosa na cavidade medular do osso maxilar, conhecida como FDOJ (Fatty degenerative osteonecrosis in the medullary space of the jawbone). É essencial entender que em qualquer manipulação do osso maxilar – por exemplo, colocação de implantes, extração dentária e de e de terceiros molares – ativa vários processos inflamatórios, que são seguidos por mecanismos fisiológicos de reparação óssea. Mas o que é a osteonecrose degenerativa do osso maxilar, ou FDOJ?

O que é exactamente FDOJ?

Quando temos presente uma inflamação crónica, esta influencia fortemente a osteoimunologia, determinando profundas alterações metabólicas, estruturais e funcionais no osso. São frequentemente descritos e discutidos na literatura científica os chamados edemas medulares ou defeitos ósseos circunscritos “focais” na mandíbula (“defeitos focais da medula osteoporótica”).

Estas cavitações da mandíbula são caracterizadas por frações necróticas da medula óssea e as osteólises degenerativas gordurosas do osso maxilar (FDOJ) podem ser dolorosas ou permanecer assintomáticas por anos. Áreas afetadas por FDOJ podem ser impactadas pela super-expressão de mediadores inflamatórios, como as quimiocinas CCL5 conhecida também como RANTES (Regulated upon Activation, Normal T-cell Expressed and presumably Secreted).

As características macroscópicas das amostras de osso FDOJ são consistentemente semelhantes. Devido ao amolecimento da substância óssea, o espaço medular pode ser curetado. A degeneração do osso esponjoso estende-se até as áreas mandibulares, chegando até o canal do nervo alveolar inferior.

Um grupo de investigação na Alemanha, com quem trabalhamos, tem vindo a documentar sobre a gravidade dessas lesões há muitos anos, nas suas publicações.

A Figura 1 é um exemplo de FDOJ onde vemos no CBCT (meio diagnóstico essencial para detetar a presença de cavitações) uma imagem predominantemente radiolúcida do maxilar inferior direito (4º quadrante).

Figura 1

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.

As Figuras 2 e 3 representam uma amostra de FDOJ que exibe uma transformação predominantemente gordurosa do osso maxilar tanto superior, bem como o CBCT correspondente que mostra uma área aparentemente radiolúcida no maxilar superior (dente 21).

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.

Figura 2

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

Figura 3

Super-expressão específica de RANTES/CCL5 em FDOJ e a possível conexão com doenças sistémicas

A resposta inflamatória do tecido adiposo associada a uma resposta inflamatória sistémica é bem conhecida e amplamente estudada. A secreção de quimiocinas inflamatórias medeia os efeitos sistémicos da inflamação do tecido adiposo e a maioria dos tecidos adultos normais contém poucas, se houver, células RANTES/CCL5 positivas. Em contraste, a expressão de RANTES/ CCL5 aumenta de forma significativa em locais inflamatórios.

Esses resultados indicam uma expressão mais elevada de RANTES/CCL5 do que anteriormente presente na ausência de inflamação, o que sugere que varias ações inflamatórias estão a ocorrer neste momento que aumentam a expressão deste mediador, como acontece tipicamente na FDOJ.

A redução do fluxo sanguíneo e da densidade capilar seguida de isquemia nos espaços medulares do osso maxilar pode levar a uma situação de hipoxia. Esses gatilhos levam à ativação de vias de sinalização que favorecem uma predisposição para o desenvolvimento de doenças crónicas. No geral, os sistemas de comunicação celular são organizados em cascatas com estágios sequenciados e os mensageiros de sinalização como as citoquinas carregam instruções e são recebidas por células com recetores específicos que são capazes de reconhecê-los.

Em publicações anteriores, foi definido este processo inflamatório crónico como osteonecrose degenerativa gordurosa nos espaços medulares do osso maxilar (FDOJ). Este material clínico foi obtido de pacientes que foram tratados cirurgicamente por suspeita de inflamação crónica na área da mandíbula e que o FDOJ deveria contribuir para as doenças inflamatórias sistémicas.

A incapacidade de corretamente diagnosticar esta patologia medular antes ou durante a inserção de um implante dentário, poderá explicar, em alguns casos, porque existem implantes dentários que não integram, independentemente do médico ter seguido um protocolo correcto.

A saúde oral é fundamental no diagnóstico e tratamento de doenças sistémicas

Os mediadores de sinalização pró-inflamatórios, como RANTES/CCL5, em particular, afetam o organismo sistemicamente e podem resultar em processos inflamatórios crónicos. É geralmente aceite que no caso de um desequilíbrio entre as citocinas e seus inibidores específicos, haja uma predisposição elevada para desenvolver doenças inflamatórias crónicas. Nestes casos as citoquinas juntam-se para iniciar uma resposta imune e induzir eventos inflamatórios agudos, até criar uma inflamação crónica persistente. Isso significa que, para manter condições saudáveis, os mecanismos de produção de citoquinas devem ser controlados. Para isso é necessário perceber qual é a origem e o gatilho que desencadeia a produção destas citoquinas, e que é possível que a origem seja dentária. Por esse motivo, uma vez mais a saúde oral tem um papel preponderante no diagnóstico e tratamento de doenças sistémicas.

O FDOJ representa um novo fenómeno de resposta inflamatória celular em que as citoquinas não são desencadeadas pela presença de bactérias ou vírus. Assim, formulamos a hipótese de que a sinalização RANTES/CCL5 é um distúrbio crónico tipicamente derivado de áreas FDOJ que podem contribuir para o desenvolvimento de inflamações crónicas.

*Dr. Miguel Stanley, Fundador e Director Clínico da White Clinic
*Dra. Ana Paz, Ciência, Investigação e Actividade Clínica na White Clinic