Nonsurgical Adjunctive Therapies for the Management of Periodontal Disease

Alison Glascoe, DDS, MS

October 2015 Course - Expires October 31st, 2018

American Academy of Periodontology


Periodontal disease is a general term used to describe an infectious inflammatory process that may involve one or more structures of the periodontium. Dental plaque, or plaque biofilm, is the primary etiologic agent for periodontal disease. A pathologically and destructive host-inflammatory response occurs due to the bacterial challenge, resulting in the clinical expression of disease. Numerous therapies have evolved in the treatment and management of periodontal disease, including the use of systemic and local-delivery antibiotics, antimicrobial mouth rinses, and host-modulatory therapies.

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Periodontal disease is a general term used to describe an infectious inflammatory process that may involve one or more structures of the periodontium. The supporting structures of the teeth, also known as the attachment apparatus, include the alveolar bone, periodontal ligament, and root cementum. Periodontal disease is perhaps the most common chronic infection1 and is caused by dental plaque, or plaque biofilm, which is the well-organized, heterogeneous structure composed of microbial pathogens.

More than 500 microbial species are thought to be the primary etiologic agents.2 In addition, viruses and fungi are also associated as putative pathogens.2 In disease, the putative periodontal pathogens reside in and colonize the gingival tissue collar that surrounds the tooth, forming the periodontal pocket. Up to 109 bacteria may be harbored in the deeper periodontal pockets.3 Despite the potential for many pathogens to be associated with periodontal disease, a small number are most frequently linked with active periodontal disease.

Socransky et al4 divided the pathogens into two main clusters of microorganisms and deemed them the “red” and “orange” complexes. The red complex includes the following Gram-negative anaerobic pathagens: Porphyromonas gingivalis, Treponema denticola, and Tanneralla forsythia. The orange complex includes Fusobacterium nucleatum, Prevotella intermedia, Prevotella nigrescens, Peptostreptococcus micros, Campylobacter rectus, Centruroides gracilis, Campylobacter showae, Eubacterium nodatum, and Streptococcus constellatus. Other microbial pathogens highly associated with periodontal disease are Aggregatibacter actinomycetemcomitans and Eikenella corrodens. These findings suggest that therapies targeting these pathogens should be a goal in the management of periodontal disease.


Systemic antibiotic therapy should be considered in many clinical conditions in the management of the patient with periodontitis. This might apply in the following refractory periodontitis cases in which the patient has not responded to conventional therapy and the diagnosis has been confirmed: for a patient with an abscess, for someone who is immunocompromised or immunosuppressed, for an individual with uncontrolled diabetes mellitus, and for a patient with signs and symptoms of systemic involvements, fever, and lymphadenapathy.5

The selection of the most appropriate systemic antibiotic should be based on findings from culture and sensitivity testing. Such testing would determine which microbial pathogens are present in order to determine the most appropriate antibiotics. Systemic antibiotic therapy should never be used as a monotherapy for the treatment of periodontal disease and should always be prescribed as part of a comprehensive examination, diagnosis, and treatment plan.

Using systemic antibiotic therapy has advantages and disadvantages. Because it is considered conventional, patients are familiar with taking systemic antibiotics and generally accept this treatment.5 A disadvantage to systemic antibiotic treatment includes patient noncompliance.5 Patients may forget to take the medication or do not take it as prescribed. In addition, systemic antibiotics have the potential for causing adverse gastrointestinal effects, such as diarrhea and cramping.5 Other possible negative issues are allergic reactions and the potential for bacteria developing resistance to antibiotics over time.6,7 Bacterial resistance is a major concern in healthcare today, so providers must carefully weigh the risks-versus-benefits ratio.

Systemic antibiotics reach the periodontal tissues by transudation from the serum, then cross the junctional and crevicular epithelium to enter into the gingival sulcus.6 The effective concentration of the antibiotic when it reaches the gingival sulcus when taken systemically is not the same as it might be for another infected site in the body.

Several systemic antibiotic regimens have been used in the treatment of periodontal disease. Typically, they are used in conjunction with subgingival mechanical instrumentation with removal of supragingival plaque deposits. These practices, when used with effective oral home care, are aimed to reduce the bacterial load at the gingival margin, as well as above and below the gingival margin.

Some commonly prescribed systemic antibiotic regimens used for the treatment and management of periodontal disease include amoxicillin (375 mg) and metronidazole (500 mg) taken 3 times a day for 7 days in conjunction with full-mouth scaling and root planing (SRP) performed within 48 hours.6 This regimen has been shown to reduce periodontal pocket depth and bleeding on probing compared to controls,6,8-10 which are the desired outcomes for the treatment of periodontal disease. Another regimen, azithromycin (500 mg) taken for 3 days prior to full-mouth (SRP), has been shown to reduce the bacterial load of the red complex microbes and lower the gingival index.6,11

In the absence of culture and sensitivity testing, the use of systemic antibiotics empirically to treat periodontal disease may be considered. Reasonable choices include the combination of amoxicillin and metronidazole (250 mg to 500 mg of each) taken 3 times a day for 8 days or the combination of metronidazole and ciprofloxacin (500 mg of each) taken 2 times a day for 8 days.6

Local antibiotic therapy is an alternative adjunctive treatment option to be considered in the management of periodontal disease. This therapy consists of the delivery of an antibiotic directly into the periodontal pocket where pathogens are colonized.5 The concentration of the antibiotic is amplified when delivered directly into the periodontal environment. An advantage of local-delivery antibiotic therapy over systemic antibiotics is the lack of the potential development of gastrointestinal distress and allergic reaction.5

The first local-delivery antibiotic system to be used was Actisite™ (tetracycline periodontal).12 No longer available in the United States, it consisted of nonresorbable tetracycline-impregnated fibers that were placed directly into the periodontal pocket.12,13 The fiber was to remain in the periodontal pocket for 10 days before the practitioner removed it at a second appointment.

Developments of resorbable local-delivery products and advancements in delivery systems have improved the management of the disease. Atridox® (Denmat, is the first resorbable local-delivery antibiotic system13 and consists of doxycycline in a gel form, which is applied with a syringe to the tooth pocket. It then hardens when in contact with saliva into a wax-like material, allowing the antibiotic to be slowly released over 21 days.

Arestin® (Orapharma, was the next resorbable local-delivery antibiotic to be marketed. Arestin consists of minocycline spheres in a powder supplied in a single-dose ampule loaded onto a syringe.13 The powder is expressed directly into the periodontal pocket. The antibiotic maintains therapeutic levels for 14 days and stays in the periodontal pocket for 28 days.13

Studies have shown that when local-delivery antibiotics are used in conjunction with SRP, clinical outcomes are favorable.6,13,14 The findings suggest a reduction in periodontal pocket depth and improvement in clinical attachment levels.

Antimicrobial Mouth Rinses

Antimicrobial mouth rinses are commonly used by consumers and seem to be most effective when used as adjuncts to control gingival inflammation. An example would be in acute situations when a patient’s ability to perform optimal oral home care has been interrupted, such as during the postsurgical period.

When trying to determine which oral healthcare product to use in an effort to control supragingival plaque levels and gingival inflammation, the general public is advised to look for the American Dental Association Seal of Acceptance. This means that findings from clinical, biologic, and laboratory testing have shown that the product reduces gingivitis and supragingival plaque levels.6 However, this statement is not a guideline for the management of periodontitis or other forms of periodontal disease. The only antimicrobial mouth rinses on the market with the seal are those with phenolic compounds such as Listerine® and its generic versions.

Considered the gold standard for antimicrobial mouth rinses,15 chlorohexidine gluconate (0.12%) is available in the United States by prescription only and is known as Peridex™ and PerioGuard® (Colgate-Palmolive, Chlorohexidine is the most effective antimicrobial oral rinse at reducing bacteria and for the treatment of gingivitis.16 It works better against Gram-positive bacteria and some yeast and is less effective for combating Gram-negative bacteria. It is commonly prescribed postoperatively to lower bacterial biofilm loads during healing. Chlorohexidine has high substantivity, which means its effects are prolonged.17 Some adverse effects associated with chlorohexidine use include the potential for staining of the teeth and dorsum of the tongue; altered taste perception; and an increase for the development of supragingival calculus formation, mucositis, and desquamation of the epithelium.6,18,19

Other antimicrobial rinses available to the general public and less often recommended by practitioners include quaternary ammonium compounds such as Cepacol® (Reckitt Benckiser, Sanguinarine-based products such as Viadent™ are no longer on the market.

Products with oxygenating agents such as hydrogen peroxide are recommended more frequently in the paste form. These products do exhibit anti-inflammatory properties resulting in less bleeding on probing, which is a critical clinical indicator for periodontal inflammation; however, they have little effect on reducing bacterial levels.6,20 Today, concerns have been raised regarding the potential for carcinogenicity and tissue injury.6,21

Triclosan is another antimicrobial agent and is found in toothpastes and mouth rinses. However, studies have shown that it has little effect on changing oral microbial flora,6,22,23 and significant concerns have been raised regarding the safety of triclosan.24

Anti-inflammatory Agents

Studies have been conducted assessing the use of anti-inflammatory agents in the management of periodontal disease. We must remember that periodontal disease is an infectious, inflammatory disease resulting in a host-immune response to a microbial challenge. In inflamed tissues, as noted with periodontal disease, periodontal microbial pathogens proliferate. This can result in a pathologic and destructive inflammatory process, through the activation of the body’s host defense cells, which include macrophages and their precursors, monocytes, lymphocytes, and polymorphonuclear leukocytes, or PMNs (such as neutrophils).25 Microbial components, such as lipopolysaccharide, found in the cell walls of Gram-negative anaerobic microbes, activate macrophages to produce and secrete proinflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α).25 IL-1 promotes bone resorption. It also stimulates the release of PGE2 by fibroblasts, which are the primary and most abundant cell type found in connective tissue.5 Fibroblasts synthesize collagen, the main structural protein of connective tissue.5 Collagen is also the main fiber component of gingival tissue and bone, which are supportive structures necessary for periodontal health.5

Fibroblasts and inflammatory cells (neutrophils and macrophages) synthesize matrix metalloproteinases (MMP), which are enzymes or proteins that facilitate biologic reactions. For example, MMP-1 and MMP-8 are enzymes that degrade collagen, which weakens periodontal support.5 Activation of the immune sytem is the body’s way to protect itself against a pathogenic challenge; however, the result is often damaging to the host through destruction of tissue. This is due to the release of cytokines, proinflammatory mediators, and MMPs. These agents not only act locally, affecting the periodontal tissuses, but once in the systemic circulation they induce and perpetuate systemic effects.

MMPs are a group of proteolytic enzymes found in the periodontal tissues. Various MMPs include collagenases and gelatinases. These enzymes function to remodel the extracellular matrices of periodontal tissues.6,26 Because researchers have found that subantimicrobial doxycycline has anticollagenolytic properties, they have proposed its use as a host-modulating agent in the treatment of periodontal disease.6,27 A subantimicrobial dose of doxycycline (20 mg twice a day) was found to be effective in inhibiting collagenase activity without contributing to antimicrobial resistance when used in conjunction with SRP, as denoted by a gain in clinical attachment levels and a reduction in periodontal probing pocket depths.6,28,29

Oral Medications

Nonsteroidal anti-inflammatory drugs (NSAIDs) have also been studied as inhibitors of the host response in the management of periodontal disease. The mechanism of action is prevention of prostanoid formation.6 Prostaglandin E2 (PGE2) is associated with inflammation and bone resorption and is elevated in periodontal disease.30 Researchers have studied different NSAIDs, such as flurbiprofen, ibuprofen, ketorolac, naproxen, and aspirin administered both systemically and locally, and found that, when combined with SRP, alveolar bone height was maintained.6,28

Bisphosphonates are a class of drugs that inhibit alveolar bone resorption31 and have been used as host-modulatory agents in the treatment of periodontal disease. Studies have shown that bisphosphonate therapy, when employed in conjunction with SRP, has resulted in a reduction in periodontal probing depths, a gain in clinical attachment, a reduction on bleeding on probing, and an increase in alveolar crestal bone height.6,32-34

Despite the potential benefits of bisphosphonate therapy, studies have shown that long-term use and high doses have been associated with osteonecrosis of the jaw.6,35,36 Further studies are needed to determine whether the potential benefits of bisphosphonate therapy outweigh the relative risks when used in the management of periodontal disease.

Host-Modulatory Therapies

Locally administered host-modulatory agents, such as enamel matrix proteins, bone morphogenetic protein, and platelet-derived growth factor, have been used in the treatment of periodontal disease. Enamel matrix protein, available as Emdogain™ (Straumann,, has been used to treat periodontal defects.37 Enamel matrix protein is supposed to act as a tissue-healing modulator to stimulate periodontal regeneration and to regenerate all components of the attachment apparatus.38-40 Bone morphogenetic protein modulates and differentiates mesenchymal cells into bone. It acts as a scaffold onto which new bone can grow and is often used with guided-bone regenerative procedures such as alveolar ridge augmentation in preparation for dental implants.38,41 Finally, platelet-derived growth factor works to increase chemotaxis of neutrophils and monocytes, stimulate the proliferation of fibroblasts, increase extracellular matrix synthesis, and increase the differentiation of mesenchymal progenitor cells, fibroblasts, and endothelial cells.38,42 It is used most often in periodontal surgical regenerative procedures.


As we learn more about host-bacterial interactions and the host immune-inflammatory responses resulting in periodontal breakdown and destruction, we will build on our current concepts and treatment modalities using systemic and local delivery antibiotics, antimicrobial rinses, and host-modulatory therapy. Further research and studies will elucidate additional adjunctive therapies that may be used in the treatment and management of periodontal disease.

About the Author

Alison Glascoe, DDS, MS, is an associate professor in the Department of Periodontics and Preventive Services at Howard University College of Dentistry in Washington, DC.


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SOURCE: CDEWorld | October 2015

Learning Objectives:

  • Explain the use of systemic antibiotics in the management and treatment of periodontal disease.
  • Describe the use of local-delivery antibiotics in periodontal disease.
  • Discuss the use of host-modulatory therapy in periodontal disease.