Host Modulation PDF

31.10.2023 Host Modulation Assisst. Prof. Ece RAKUNT TOPTAŞ School of Dental Medicine Department of Periodontology Istanbul [email protected] 1 Newman and Carranza`s Clinical Periodontology Newman Takei Klokkevold Carranza Chapter 54 2 1 31.10.2023 Host Modulation Host organism whi...

31.10.2023 Host Modulation Assisst. Prof. Ece RAKUNT TOPTAŞ School of Dental Medicine Department of Periodontology Istanbul [email protected] 1 Newman and Carranza`s Clinical Periodontology Newman Takei Klokkevold Carranza Chapter 54 2 1 31.10.2023 Host Modulation Host organism which a parasite obtains its nourishment from or in the transplantation of tissue the individual who receives the graft Modulation alteration of function/status of something in response to a stimulus 3 Systemic Diseases, Genetic, Hormonal and Environmental Factors X Microbial Dental Phase I Periodontal Therapy Plaque Host Response 4 2 31.10.2023 Host modulation therapy (HMT): a treatment concept that aims to change the status or function of the host to treat the disease In periodontitis; v HMT aims to manipulate the immune response with chemotherapeutic agents and prevent/reduce tissue destruction. 5 Subgingival plaque bacteria accumulate LPS, microbial peptides, bacterial antigens diffuse into gingival connective tissues Vasodilation and permeability increases in the gingiva Epithelial and connective tissue cells produce inflammatory mediators Fluid accumulates in the tissues Defense cells migrate from the circulation 6 3 31.10.2023 Ø Neutrophils, macrophages, T lymphocytes, B lymphocytes, plasma cells Ø Matrix metalloprototeinases (MMPs) break down collagen fibers resulting the destruction of periodontal ligament Ø Cytokines (interleukins and TNF-𝛼 ), prostaglandins (PGE2) stimulate osteoclasts to resorb alveolar bone Pro-inflammatory mediators With HMT Protective/antiinflammatory mediators 7 With successful HMT; Reduce excessive/pathologically elevated inflammatory process Block normal defense mechanism Reduce excessive levels of enzymes, cytokines and prostaglandins Reduce levels below constitutive levels Modulate osteoclast and osteoblast function Affect normal tissue turnover 8 4 31.10.2023 v Nonsteroidal Antiinflammatory Drugs (NSAID) ØThese drugs are used to treat pain, acute inflammation, and some chronic inflammatory conditions ØSalicylates (aspirin) and indomethacin and propionic acid derivatives (ibuprofen, naproxen) NSAIDs Blocks Prostaglandin (PGE2) production Inflammation reduce Osteoclast activity inhibition 9 Nonsteroidal Antiinflammatory Drugs NSAIDs; •Reduce periodontal attachment loss •Slow the rate of alveolar bone loss ØHas significant side effects L üGastrointestinal problems üHemorrhage üRenal and hepatic impairment üWhen drug taken is stopped bone loss rate turns back to normal/increases (rebound effect) 03/11/2022 Host Modulation © Dr. Fatma ONER 10 5 31.10.2023 vBisphosphonates ØBone-seeking agents à inhibit bone resorption by disrupting osteoclast activity, promote osteoblastic activity ØReduces alveolar bone loss and increases density of bone ØUsed in the management of osteoporosis and bone-resorptive pathologies ØBut has side effects of: üInhibiting bone calcification üChanging white blood cell counts üAvascular necrosis of the jaws increase the risk of bone necrosis after dental extractions(BRONJ/ONJ) 11 vBisphosphonates ØSystemic bisphosphonates (oral/parenteral) adjuncts to SRP were not better than SRP alone, no protection against bone loss Both NSAIDs (local and systemic) and Bisphosphonates are not approved as adjunct treatment of periodontal diseases!! 12 6 31.10.2023 v Sub-antimicrobial-Dose Doxycyline (SDD) ØSDD (Periostat) is the only drug approved by the U.S. Food and Drug Administration (FDA) and American Dental Association (ADA) ØSDD is 20-mg dose of doxycycline, 2X1 from 3 to 9-24 months ØIt does not have antimicrobial effect on the oral/bacterial flora ØIt exerts its effect by enzyme, cytokine and osteoclast inhibition no antibiotic effect xxx Studies show that adjunct treatment with SDD show more clinical benefits than mechanical therapy alone (in terms of bleeding on probing, decreasing probing depth, regaining CAL and biochemical efficiacy) 13 Mechanisms of Action Ø Doxycycline à tetracycline family Ø Doxycycline à down-regulates the activity of MMPs by reducing cytokine levels à Stimulates osteoblastic activity and new bone formation by up- regulating collagen production Ø It should be used at least 3 months to prevent rebound effect and for prolonged drug effect Ø Studies have shown that no overgrowth of opportunistic pathogens (Candida) in the oral cavity, gastrointestinal/genitourinary system 14 7 31.10.2023 INDICATIONS: Patients with aggressive periodontitis being treated non-surgically Patients with chronic periodontitis who are refractory to non-surgical treatment Patients having periodontal surgery Smoking patients Patients with genetic susceptibility Patients with diabetes, osteoporosis Ø SDD should not be used in gingivitis and acute periodontal conditions!!!! 15 Contraindications Patient with a history of allergy or hypersensitivity to tetracycline Pregnant/lactating woman (potential for discoloration of the developing tooth) Children younger than 12 Ø Patient selection is important (motivation to oral hygiene and willingness to take systemic drug)!!!!! ØSDD is adjunct to mechanical periodontal therapy not a stand-alone treatment or monotherapy 16 8 31.10.2023 17 18 9 31.10.2023 v Probiotics ØProbiotics are live, non-pathogenic microorganisms used to improve microbial balance, particularly in gastrointestinal tract Ø Lactobacillus and Bifidobacterium genera-based probiotics are used adjunct to SRP ü Microbiome modulation and pathogen suppression ü Inhibit inflammatory pathways ü Promote activity of regulator cells ü Improve epithelial barrier function ü Enhance protection of host cells against physiologic stress 19 Probiotics + Mechanical Plaque Removal ØMost clinical studies reported additional improvements in decreasing periopathogens rather than host modulation Ø No adverse effect in healthy people Clinical Benefits (probing depth, CAL gain) No difference Ø Higher risk of infection (bacteremia/fungemia) in patients critically ill, hospitalized or immunocompromised Ø The clinical efficacy, safety and host modulatory potentials should be further established with longer clinical trials 20 10 31.10.2023 v Statins Ø Statins are used to manage hyperlipidemia for the prevention of cardiovascular diseases Ø Inhibit enzyme activity Ø Increase the expression of bone morphogenetic protein Ø Increase vascular endothelial factor Ø Systemically administered statins Induce proliferation and differentiation of osteoblasts promoting bone formation No improvements Ø Topical application in gel form in deep pockets clinical benefits The data supporting the topical application of statins in periodontal defects originate mainly from one research group and have not been independently reproduced 21 v Topical Bisphosphonates Topical application of bisphosphonate (1% alendronate gel, ALN) + SRP Reduction of periodontal pocket depth Regaining clinical attachment levels Bone fill of intrabony defects Ø No adverse effects have been reported Ø Studies originate from one group and needs to be independently reproduced 22 11 31.10.2023 v Specialized Pro-Resolving Mediators (SPMs) Omega 3 fatty acids (fish oil) Enzymatic reactions Resolvins, Lipoxins, Maresins, Protectins ØSPMs initiate proresolving pathways and promote the termination of inflammation for restoration of tissue homeostasis Ø Topical application Ø Systemic application Animal models 23 vSpecialized Pro-Resolving Mediators (SPMs) ØTopical application of SPMs; ü Prevent alveolar bone resorption ü Regenerate lost bone due to periodontal inflammation ü Decreases inflammatory infiltrate ü Promotes a host-mediated shift in the subgingival microflora reversing dysbiosis Ø Systemic application of SPMs; ü Regulate immune response Now, SPMs are seen ideal future drug candidates due to animal studies. But clinical studies are necessary 24 12 31.10.2023 25 13