Host Modulation Therapy

Host modulation therapy is recommended as an adjunct to scaling and root planing in the periodontal therapy. The basic purpose of host modulation therapy is to restore the balance between pro-inflammatory and anti-inflammatory mediators.

1. HOST MODULATION THERAPY -Dr.Shraddha Kode

2. INTRODUCTION Definition: Host modulation therapy (HMT) is a treatment concept that aims to reduce tissue destruction and stabilise or regenerate the periodontium by modifying or downregulating destructive aspects of the host response and upregulating protective or regenerative responses 2

3. Balance exists between pro-inflammatory and anti-inflammatory mediators In case of a progressive periodontitis lesion – balance is skewed towards the predominance of pro-inflammatory mediators Therefore, it becomes essential to restore this balance 3

4. 4 PURPOSE To restore the balance between pro-inflammatory and anti-inflammatory mediators HMT can be systemically administered or locally delivered It is used as an adjunct to scaling and root planing

5. 5 When to give HMT? Individuals at high risk for development of severe periodontitis Smokers Diabetics those who are positive for IL-1 genotype Golub & Williams – pioneers of HMT in periodontics – diabetic rats – excess of collagenase activity – improvement in gingival health of rats treated with tetracycline

6. CLASSIFICATION

7. 7 HMT MODULATION OF IMMUNE RESPONSE MODULATION OF ARACHIDONIC ACID METABOLITES MODULATION OF BONE REMODELLING HMT PROMOTING PERIODONTAL REGENERATION MODULATION OF NITRIC OXIDE SYNTHASE ACTIVITY MODULATION OF CELL SIGNALING PATHWAYS

8. MODULATION OF IMMUNE RESPONSE

9. 9 PRO-INFLAMMATORY CYTOKINE INHIBITION IL-1, IL-6 & TNF- α – elevated in diseased periodontium – amplify inflammatory condition Pentoxifylline – methylxanthine derivative – blocks synthesis of TNF-a Recombinanant IL-11 – inhibits production of TNF-a, IL-1 and NO

10. 10 MODULATION OF MATRIX METALLOPROTEINASE (MMP) ACTIVITIES MMPS – zinc & calcium dependant endopeptidases secreted by neutrophils , macrophages, fibroblasts, epithelial cells – include collagenases , gelatinases & metalloelastases Golub et al 1983 – discovered anti- collagenase activity of tetracyclines

11. 11 PERIOSTAT – formulation of sub-antimicrobial dose (SDD) of Doxycycline Hyclate 20mg – twice daily for a period of 3-9 months – effectively lowers down MMP levels Advantages of Doxycycline: downregulates inflammatory cytokines, scavenger of reactive oxygen species, stimulates collagen production, reduces bone resorption

12. MODULATION OF ARACHIDONIC ACID METABOLITES

13. 13 NONSTEROIDAL ANTI-INFLAMMATORY DRUGS Arachidonic acid metabolism – cyclooxygenase pathway produces prostaglandins – pro-inflammatory activity – destructive NSAID’s – inhibit cyclooxygenase – prevents production of arachidonic acid metabolites – inhibit gingivitis & prevents progression of periodontitis

14. 14 LIPOXINS & RESOLVINS Bacteria & bacterial products like lipopolysaccharides – initiate inflammatory response – pro-inflammatory mediators Anti-inflammatory mediators are also produced during these interactions – lipoxins , resolvins , docosatrienes , neuroprotectins

15. MODULATION OF BONE REMODELLING

16. 16 BISPHOSPHONATES Periodontitis – characterized by alveolar bone loss; therapeutic modality of host modulation – stop alveolar bone resorption Bisphosphonates – management of bone disorders like osteoporosis & Paget’s disease – inhibits bone resorption & maintains bone density , downregulate MMP’s – MMP-3, MMP-8, MMP-13

17. 3 GENERATIONS OF BISPHOSPHONATES 17 FI 1 FIRST GENERATION Etidronate, Clodronate 2 Alendronate, Pamidronate (100-1000 times more potent than 1 st generation) 3 THIRD GENERATION SECOND GENERATION Risedronate, Ibandronate (10,000-1,00,000 times more potent than 1 st generation) Alendronate – research work – preserves alveolar bone resorption, anti-inflammatory & anti-bacterial effects – improvement of periodontal status & bone turnover in postmenopausal women

18. 18 CHEMICALLY MODIFIED TETRACYCLINES (CMT’s) CMT’s – derivatives of tetracycline group of drugs – lack antimicrobial action but potent host modulating effects Inhibit MMP’s – inhibit bone resorption in periodontitis CMT’s – therapeutic agents in periodontitis

19. 19 HORMONAL REPLACEMENT THERAPY FOR POST-MENOPAUSAL WOMEN Osteoporosis – major health problem in post-menopausal women – low estrogen production – decrease in bone mineral density – induces bone resorption Symptoms – reduction in epithelial keratinisation, dry mouth, redness & abnormal paleness of gingival tissues, altered taste sensation HRT – relieve these symptoms & improve the quality of life

20. HOST MODULATION BY PROMOTING PERIODONTAL REGENERATION

21. Root conditioning Growth factors & hormones – Platelet rich plasma (PRP), Platelet rich fibrin (PRF), Enamel matrix derivatives (EMD), Bone morphogenetic proteins (BMPs) 21

22. MODULATION OF NITRIC OXIDE SYNTHASE (NOS) ACTIVITY

23. Nitric oxide (NO) – free radical – toxic when present in high concentrations – implicated in a variety of inflammatory conditions Nitric oxide synthase inhibitors – non-selective: not specific to any kind of NOS whereas selective – specific Selective – mercaptoethylguanidine (MEG) and guanidinoethyldisulfide (GED) – potent inhibitors – scavenge NO – inhibit prostaglandin production 23

24. MODULATION OF CELL SIGNALLING PATHWAYS IN PERIODONTAL DISEASES

25. 25 Host-bacterial interaction – generation of inflammatory response – connective tissue destruction Activation by cell signaling mechanisms Periodontal disease – most important pathways – mitogen activated protein kinase ( MAPK ), nuclear factor kappa B ( NF- kB ) & Janus tyrosine kinase signal transducer and activator of transcription ( JAK/STAT ) Inhibition of these pathways – reduction in synthesis of pro-inflammatory mediators -

26. 26 LIMITATIONS OF HMT Long duration of therapy Side effects (ex. Bisphosphonates related osteonecrosis of jaws) Lack of long term studies

27. 27 CONCLUSION In medically compromised patients, smokers, genetically predisposed individuals, recurrent periodontitis – host modulation therapy is desirable along with conventional treatment Long term clinical trials are essential to authenticate their long and safe use on patients

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