HOST MODULATION IN PERIODONTICS PDF
antimicrobial dose doxycycline and Non-Surgical. Periodontal Therapy. The main outcomes sought were host modulation therapeutics in periodontics. Exclusion. ABSTRACT. The etiology of chronic periodontitis involves complex host-parasite interactions modified by environmental and genetic factors. Contemporary. 1Department of Periodontology, Government Dental College and Research Institute Host modulation therapy has emerged in recent years as.
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Register Lost your password? As already discussed in the previous chapters, the primary etiology of periodontal diseases is bacterial infection 1. In addition to bacterial etiology, the progression of periodontal diseases is adversely influenced by a number of risk factors and risk indicators like diabetes, gender, age, hereditary factors and smoking 2. Traditional treatments focused on reducing the bacterial load through scaling and root planning, but they were not effective in every patient.
Host modulation therapy HMT is a treatment concept that aims to reduce tissue destruction and stabilize or even regenerate the periodontium by modifying or down-regulating destructive aspects of the host response and up-regulating protective or regenerative responses.
The purpose of HMT is to restore the balance, on one hand, periodontice pro-inflammatory and anti-inflammatory mediators and on the other hand between destructive enzymes and their inhibitors. They can be systemically administered or locally delivered and used as adjuncts to scaling and root planning 4. The underlying biological mechanisms of this response are characterized by the expression of endothelial cell and intercellular adhesion molecules and by the production of hosg inflammatory mediators, including, cytokines and lipids by neutrophils, monocytes, lymphocytes and fibroblasts.
The balance between inflammatory mediators and their counter-regulatory molecules is crucial for determining the outcome of the immuno-inflammatory pathology of periodontal diseases.
In the case of stable gingivitis lesion, the pro- and anti-inflammatory response is supposed to be in balance, whereas the response is skewed towards the predominance of pro-inflammatory reactivity in progressive periodontixs lesion.
As present data suggest that periodontal diseases have got a multi-factorial etiology, the risk factors are equally important in the final outcome of the disease progression. Before we go through the therapeutic agents used in host modulation, let us first try to understand the steps where these agents modulate the host response.
Host modulatory therapy
Many studies have indicated that the biological activity of a variety of cytokines may be directly relevant to periodontal destruction 7, 8. IL-1, IL-6, and tumor necrosis factor TNF have all been found to be significantly elevated in diseased periodontal sites as compared to healthy or inactive sites Cytokines have a synergistic effect.
Acting together pro-inflammatory cytokines amplify the inflammatory condition. As already explained in the previous sections, the balance between the pro and anti-inflammatory cytokines is crucial in the periodontal health and disease. Imbalances between these mediators in the periodontal tissues are a major cause of periodontal destruction Pentoxifylline PTX is a ……………………. Buy Now For International Users: The activity of MMPs can be modulated by various ways which include, modulation of the production of MMPs, blocking activation of the proenzyme, blocking the activity of the enzyme, and activating MMP inhibitors The MMPs are a family of zinc- and calcium-dependent endopeptidases secreted or released by a variety of infiltrating cells i.
MMPs include collagenases, gelatinases, and metallo-elastases. MMPs have been strongly associated with periodontitisand excellent reviews have been published discussing the role of MMPs in periodontal diseases 22, While experimenting on germ-free diabetic rats Golub et al.
Ten different chemically modified tetracyclines CMTs have been developed, 9 of which inhibit MMPs and do not possess antimicrobial properties In further studies using these different tetracyclines, Golub et al 34 reported that……………. It is indicated as an adjunct to scaling and root planning SRP taken twice daily for a period of months in the treatment of chronic periodontitis.
Various effects of sub-antimicrobial dose of Doxycycline on host response have been enumerated in Table A lot of research work has been done on SDD. Bleeding on probing was not assessed in the meta-analysis but, in general, SDD did not improve this parameter when compared to placebo.
No significant adverse effects were reported in any of the studies. As far as bacterial resistance to the drug therapy is concerned, the resistance associated with low-dose doxycycline therapy has not been seen The fact that NSAIDs can suppress alveolar bone resorption suggests that the synthesis of arachidonic acid metabolites may represent a critical regulatory pathway for potentially blocking periodontal disease progression activity In arachidonic acid metabolism, the cyclooxygenase pathway produces prostaglandins, prostacyclin, and thromboxane, called prostanoids.
Some prostanoids have pro-inflammatory properties and have been associated with the destructive process in the inflammatory diseases. In periodontal diseases, Prostaglandin E2 PGE2 has been extensively correlated to inflammation and bone resorption 5.
Multiple NSAIDs, including indomethacin 45flurbiprofen 46ibuprofen 47naproxen 48meclofenamic acid 49and piroxicam 50 have demonstrated the ability to inhibit gingivitis 50 and progression of periodontitis in both ligature-induced 45, 51 and naturally occurring periodontal disease in animal models Bacteria and their products like lipopolysaccharides LPS initiate an inflammatory response when they are countered by the protective host response.
These include lipoxins, aspirin-triggered epi-lipoxins ATLsresolvins, docosatrienes, and neuroprotectins. These mediators can be inhibited by NSAIDs, which include various drugs such as aspirin, ibuprofen, ketorolac, flurbiprofen, naproxen, etc. Periodontitis is characterized by the alveolar bone loss. One of the therapeutic modality of host modulation is to stop the alveolar bone resorption. They have a primary indication of inhibiting bone resorption and thereby maintaining bone density They are used widely in conditions such as neoplastic hypercalcemia, multiple myeloma, and bone metastases secondary to breast and prostate cancer, suggesting a direct antitumor effect of bisphosphonates.
Chemically bisphosphonates are pyrophosphate analogs characterized by two C-P bonds Figure These drugs can be subdivided into the nitrogen-containing bisphosphonates and non-nitrogen-containing bisphosphonates Small changes in the structure of the bisphosphonates can lead to extensive alterations in their physicochemical, biological, therapeutic, and toxicological characteristics.
Bisphosphonates are classified into three generations according to the R1 and R2 groups present in their chemical structure Table R2 group contains nitrogen but within a heterocyclic group.
Bisphosphonates work by inhibiting the precipitation of calcium phosphate even at very low concentration They also slow down the dissolution of these crystals All these effects appear to be related to the marked affinity of these compounds for the solid-phase calcium phosphate to which they bind These compounds inhibit osteoclastic activity by blocking acidification by local release and represent a class of chemical structures related to pyrophosphates The effects of bisphosphonates at tissue level, cellular level, and molecular level are summarized in Table A serious adverse effect of bisphosphonates that has substantial dental implications is osteonecrosis of the jaws Table.
Good dental hygiene reduces the risk of osteonecrosis. A lot of research work has been done on bisphosphonates and periodontitis. Sodium alendronate treatment in experimental periodontitis in Wistar rats was studied and the results showed that sodium alendronate preserves alveolar bone resorption and has anti-inflammatory and antibacterial activities in experimental periodontitis MMP Inhibition and down-regulation by bisphosphonates has also been demonstrated in one study, which observed the inhibition of MMP-1, -2, -3, -7, -8, -9, and by clodronate, alendronate, pamidronate, zoledronate, and inordinate Recent studies have demonstrated that osseointegration of titanium implants can be significantly reinforced with a nanostructure treated with anodic oxidation and heat treatment.
Results showed that surface loading with bisphosphonates significantly improved the degree of osseointegration of titanium implants with a nanostructure As it is well established that CMTs inhibit the MMPs so are indirectly involved in inhibition of bone resorption in periodontal diseases. The endocrine system plays an important role in the homeostasis of the periodontium Osteoporosis, which is defined as a systemic condition characterized by a decrease in the bone mineral density by at least 2.
It is a major cause of morbidity and mortality in post menopause women. The American Academy of Periodontology considers osteoporosis to be a risk factor for periodontal disease Hormone replacement therapy HRT is used to relieve these symptoms and improve the quality of life of peri- or post-menopausal women 80, Many studies have suggested that using HRT in post-menopausal women can decrease the periodontal destruction 79, 82 and increase tooth retention Root surface conditioning, growth factors, and cytokines can be used to promote periodontal regeneration.
Growth factors and hormones, including platelet-rich plasma PRPbone morphogenic proteins BMPsplatelet-derived growth factor PDGFparathyroid hormone PTHand enamel matrix derivatives EMD have shown promise in enhancing regeneration, although their long-term predictability remains questionable, and their anticipated benefits are moderate 86, Since then a lot of research has been done on periodontal regeneration.
Regeneration has been broadly divided into two categories; graft associated and non-graft associated. Nitric oxide NO is a free radical involved in host defense that can be toxic when present in high concentrations and it has been implicated in a variety of inflammatory conditions.
NO is produced by a wide variety of cells and appears to be an important regulator of various physiologic processes in both animals and humans NO imbalances have been noted in a variety of chronic infectious and inflammatory conditions, including, periodontal disease Nitric oxide synthase NOS exists in the body in three distinct isoforms: The importance of NO in bone formation and remodeling has been highlighted from the observations of defective bone formation, volume, turnover, and osteoblast function in eNOS and iNOS deficient mice The role of NO in periodontal diseases has been well investigated.
LPS and other antigenic substances from putative periodontal pathogens such as Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescensand Fusobacterium nucleatum have been shown to induce the iNOS expression and NO production in murine macrophages It has been demonstrated that iNOS expression and activity is induced in gingival fibroblasts and neutrophils, following the stimulation by periodontal pathogens, cytokines, and other inflammatory mediators Along with this, neutrophils isolated from localized aggressive periodontitis patients were shown to display increased iNOS activity and subsequent chemotactic defects …………….
Host modulation therapeutic agents in periodontics –
As we know that bacterial biofilm present in the gingival sulcus around the tooth is a source of various bacterial components and products, which initiate periodontlcs host response. First of all the innate immune system counters the infection, but when not controlled, the acquired immune system is activated. Within ij a robust inflammatory response is generated, which initiates the connective tissue destruction.
Now this activation is done by various cellular signaling mechanisms, which leads to the synthesis of various cytokines and other inflammatory chemical mediators. When a signal is generated, it travels through the cytoplasm and reaches the nucleus, and ultimately the pattern of gene expression is altered by transcriptional and post-transcriptional mechanisms. Signal transduction depends on receptor-ligand interactions, which usually involves some modification on the cytoplasmic proteins associated with these receptors.
Host modulation by therapeutic agents
The most common modification associated with signal transduction is phosphorylation of specific amino acid residues by kinases, which induces a hosg change in the tri-dimensional structure of the protein. In the process of intracellular signaling, energy is transferred at every step which modulates the biological activity of the proteins involved.
The MAP kinases are a large family of protein kinases which are involved in cellular signaling pathways in various biological processes. These are involved in signal transduction of extracellular hormones, growth factors, and cytokines Periodntics are further divided into three classes: During inflammation, MAPK pathways particularly, p38 are involved in the increased expression of various cytokine genes by modulation of both transcriptional and post-transcriptional mechanisms.
Studies have demonstrated that inhibition of JNK and ERK pathways may effectively inhibit the production of pro-inflammatory mediators Furthermore, the MAPK inhibitors have been shown to be capable of reducing inflammation in inflammatory conditions like rheumatoid arthritis periodontcs periodontal disease Studies have shown that the inhibition of these signaling pathways can lead to the reduction in peruodontics synthesis of pro-inflammatory cytokines.
These findings have been demonstrated in patients with inflammatory diseases such as rheumatoid arthritis and periodontal disease However, more human trials are required to prove their efficacy as host modulation agents in periodontal diseases.