TABLE OF CONTENTS Oct 2005 - 1 comment

Atridox:(tm) A Valuable, Site-Specific Adjunct to Periodontal Therapy

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By: Cary Galler, DDS, MSD
2005-10-01

The primary objective of periodontal therapy is to assist our patients in preserving their dentitions in health and function. As one ages, there is an increasing likelihood that periodontal disease may become evident. This disease is manifested by the invasion of pathogenic bacteria into the subgingival environment. As a result, an inflammatory process can be initiated, which in many cases may lead to the loss of periodontal support in a susceptible host.1

First and foremost, periodontal care is intended to resist the development of periodontal disease. If a preventive periodontal care regimen is initiated, it is commonly successful in preserving periodontal health. However, if periodontal disease becomes evident, there are many treatment modalities available, which may retard or reverse the ravaging effects of the disease. Fundamentally, all periodontal treatment measures seek to resist the development of a pathogenic subgingival bacterial load.2

Primary periodontal therapy is directed to reduce the bacterial component of the disease. Scaling and root planing (SRP) is the current nonsurgical standard of therapy in achieving this goal. By mechanical debridement of the root surface, bacteria and their byproducts are removed from the tooth and gingival interphase.3 Mechanical therapy is an effective periodontal management technique. It is, however, challenging to perform because of restrictions in visibility and access to the deep subgingival area. As a result, SRP as a monotherapy, has limitations in achieving its goal.4

SYSTEMIC ANTIBIOTICS

The supplemental use of systemic antibiotics may provide additional periodontal benefit over SRP alone, but this treatment is not without side effects or adverse reactions attributed to the antibiotic. In addition, the potential for emergence of antibiotic resistance in the subgingival flora is a serious concern. Treatment failures may occur because of the drug's inability to achieve and maintain a therapeutic concentration specifically at the site of infection.5

LOCALIZED CONTROLLED DELIVERY

Conceptually, it appears that the direct application of an antimicrobial or antibiotic agent into the diseased periodontal sulcus would be an attractive treatment approach. Delivering an antimicrobial agent or antibiotic topically to the diseased site eliminates the systemic effect of the agent. In addition, the concentration of the drug may be delivered to the specific site in higher doses, without increased risk of side effects.6 The drug may be given at a dose 100 times above Minimum Inhibitory Concentration (MIC), thereby eradicating all susceptible bacteria at the site.

Controlled delivery of a chemotherapeutic agent into a diseased periodontal sulcus can alter the subgingival flora and may promote periodontal health.7-14 The principal therapeutic benefit of a localized periodontal delivery device is that it can selectively target therapy to the sites, which most specifically require additional treatment. Generally, it is easy to administer. Controlled delivery agents do not, by themselves, remove calculus and as such, it is best to perform controlled delivery in conjunction with SRP.

ATRIDOX(tm)

Currently, there are several periodontal localized delivery therapeutic agents available worldwide. Of these therapies, only Atridox(tm) has been approved for use in Canada by Health Canada.

Atridox(tm) is a controlled-release doxycycline gel that is applied subgingivally. Doxycycline is a semi-synthetic derivative of tetracycline. It is bacteriostatic and acts by inhibiting bacterial protein synthesis due to the disruption of transfer and messenger RNA at ribosomal sites. Doxycycline has a broad spectrum of activity and is effective against gram-positive and gram-negative aerobic and anaerobic bacteria, spirochetes and mycoplasma. Periodontal pathogens implicated in the progression of periodontal disease, such as Porphyromonas gingivalis and Bacteroides forsythus, Actinobacillus actinomycetemcomitans, Prevotella intermedia, Campylobacter rectus and Fusobacterium nucleatum are particularly susceptible to doxycycline.

Clinical use of Atridox(tm) allows the continuous activity over an extended period of time. It is initially a flowable gel which solidifies on contact with saliva, water or aqueous fluids. It can achieve gingival crevicular fluid (GCF) concentrations of 1500 ug/ml two hours following application, 1000 ug/ml at 18 hours and 140ug/ml at seven days, which is well above the minimum inhibitory concentration (MIC90) for periodontal pathogens.15

In comparison, with the use of systemic antibiotics, GFC concentrations of only 2.5ug/ml are achieved at 12 hours, and decline to .2 ug/ml at seven days. Initial concentrations of Atridox(tm) are up to 960 times greater than that of systemic doxycycline and at seven days, they are 740 times greater. Concentrations of Atridox(tm) in the saliva and blood serum remain extremely low, ensuring a considerable safety margin when this method of treatment is utilized.

Atridox(tm) has shown clinical therapeutic benefit in the treatment of chronic periodontitis. Its usage results in a gain of clinical attachment, a reduction in probing depth and in a reduction in bleeding upon probing.

Atridox has been extensively tested for safety and effectiveness. Garrett et al reported the results of two multicenter, randomized clinical trials in 1999.12 When SRP, Atridox and oral hygiene measures were compared, results showed that SRP and Atridox(tm) achieved superior results with respect to clinical attachment gain, pocket depth reduction and reduction in gingival bleeding upon probing. More favorable results were achieved in deeper pockets. Borden et al reported an overall reduction of periodontal pathogens at 180 days in patients treated by Atridox(tm).16,17 Polson et al in 1997 demonstrated that Atridox(tm) can achieve clinical attachment gains of 1.0mm, probing depth reduction of 1.8mm and an 80 percent reduction in gingival bleeding.18 Deeper pockets over 7mm. responded more favorably than shallow pockets, showing a 1.4mm attachment gain and a 2.6mm pocket depth reduction.

Although studies support the efficacy of Atridox(tm) as a monotherapy, treatment outcomes are likely superior when SRP and Atridox are used in combination. In a recent study comparing ultrasonic instrumentation and Atridox versus SRP alone, the ultrasonic and Atridox group showed clinically superior results with respect to pocket depth reduction in pockets greater than 4mm, bleeding upon probing, and in required treatment time.19

Scaling and root planing may not be totally effective in arresting the progression of periodontal disease.20-22 The introduction of a locally delivered doxycycline gel into an infected periodontal pocket may provide additional therapeutic benefit.

APPLICATION OF ATRIDOX(tm)

Atridox(tm) contains 50mg of doxycycline hyclate which is dissolved in a bioabsorbable, flowable gel delivery mechanism, based on a polymer of poly (DL - lactide) (PLA). The gel is applied into the periodontal pocket through a blunt ended cannula. It flows into the subgingival environment, adapting well to the intricate contours of the root anatomy and furcations areas. The gel will locally deliver high concentrations of doxycycline for seven days and will have a sustained effect for up to six months. The gel will be absorbed through the oral tissues and will be excreted in the urine over a four-week period.

Atridox(tm) is indicated in many clinical situations where the use of SRP alone does not result in the anticipated therapeutic outcome. It has its greatest benefit in pockets over 5mm. Patients typically receive SRP as a first line of defense against periodontal disease. In more advanced cases, periodontal surgical treatment, either resective or regenerative in nature, may be required. When a periodontal reevaluation is undertaken to assess the outcome of treatment, some sites may not respond with the expected degree of improvement. Recurrent inflammation, gingival bleeding and/or pocket depth may be evident. Re-infection of these sites can therefore be expected, if appropriate treatment is not undertaken to address these concerns. Atridox may be an important and valuable site-specific adjunct to periodontal maintenance.

INDICATIONS FOR ATRIDOX(tm)

Atridox is an appropriate therapy in patients who are medically or physically compromised and are unable to be present for protracted periodontal therapy.18 In addition, phobic patients may benefit because the treatment is only minimally invasive and may not require the use of a local anesthetic for its application.

Most importantly Atridox(tm) may be used as valuable adjunctive treatment in saving strategic and critical teeth that serve an important prosthetic role. Often, patients present with advanced and challenging periodontal dilemmas. Cases where long-span bridges are in place and a critical retainer shows periodontal breakdown are an example. In these situations, it is sometimes advantageous to control a site, free of infection, but with remaining increased probing depths and a loss of support, rather than committing the patient to extraction and the expensive replacement of a fixed restoration. This may be particularly applicable if adjacent pontic sites do not show sufficient support for the placement of dental implants (Figs. 6 & 7).

In the maxillary anterior segment, surgical reduction may cause postoperative gingival recession. Treatment with Atridox(tm) to control the periodontal site, without sacrificing the cosmetic result, may be a valuable strategy. Esthetic demands require minimal intervention, particularly around the margins of cast restorations.

Commonly, residual periodontal defects result following the extraction of third molars, especially in older patients. Typically, angular periodontal defects become evident, with the presence of deeper probing depths on the distal aspects of the second molars. Although many of these cases are surgically successful, the position of the second molar at the angle of the mandible or at the distal tuberosity in the maxillary arch imposes severe restrictions to successful surgical correction. In these situations, Atridox(tm) usage may be an important strategy to maintain a quiescent site and resist progressive periodontal destruction.

ATRIDOX(tm) DELIVERY

Atridox(tm) is shipped in a sealed pouch, containing two syringes marked as A (purple stripe- clear gel) and as B (yellow doxycycline powder). Additionally, a blunt ended cannula is dispensed (Figs. 8-13).

Proper injection of Atridox(tm) into a periodontal site assumes a short learning curve, to ensure no displacement of the material during insertion. The use of a cord-packing instrument is often very helpful to stabilize the material. After expressing a small flow of water from the air/water syringe, the instrument can be successfully removed from the material without displacement. Another option is dipping the instrument in a water-soluble gel. When the material is released from the syringe into the site, it often packs itself smoothly. On other occasions, it may be easier to inject the material incrementally, building it up slowly in volume. Rotating the cannula towards the tooth will break away any excess material that may be present. This excess may then be easily removed.

POSTOPERATIVE MANAGEMENT FOLLOWING ATRIDOX APPLICATION

Atridox(tm) material may be covered with a periodontal dressing to secure it in place. This is not an essential element in the treatment. Clinical judgment will dictate the circumstances when a pack may be useful.

Postoperatively, patients usually experience minimal difficulty following Atridox(tm) application. Some may complain of pressure discomfort at the treatment site. Others may mention a noticeable taste. Oral hygiene efforts should be restricted at the treated sites to avoid dislodging the material over the first seven days. Loss of the material after three days does not reduce the effectiveness of the procedure.

Atridox(tm) can be left to resorb or it can be removed several days later. Some clinicians prefer to pre-treat a site of active periodontal disease. This allows Atridox(tm) to provide a therapeutic benefit by reducing the inflammation and also distending the pocket. With pre-treatment, and appointing the patient within the first week after application, the site is more readily accessible. Improved direct visualization allows for better mechanical debridement, thus improving the clinical outcome.

NEWEST DEVELOPMENTS

The nature and severity of periodontal disease is mediated by complex interactions between a bacteriological insult and a susceptible host. The invasion of pathogenic bacteria is required to initiate the disease. However, the body's local and systemic response to bacterial toxins is a critical determinant in the progression of the disease.

Although the current standard of periodontal care is to utilize non-surgical and surgical strategies to counteract the disease, new evidence is emerging which suggests that chemotherapeutic agents may be successfully utilized to modulate the host response, and thereby arrest the progression of periodontal disease.

Periostat¿, recently approved for use in Canada in the treatment of periodontal disease, is one such agent. It works by reducing the activity of host-derived enzymes such as collagenase, cytokines and prostanoids. This chemotherapeutic agent appears to provide an exciting additional benefit in arresting periodontal disease and may have an important future in periodontal disease treatment. The newest research data suggests a synergistic clinical benefit when Periostat¿ is used along with Atridox(tm).23

CONCLUSION

Periodontal disease can often be successfully arrested by conventional non-surgical and surgical treatment modalities. In cases where periodontal reevaluation demonstrates that despite the best of care the disease is uncontrolled or progressive, it is incumbent upon the clinician to gain facility with adjunctive periodontal treatment measures. Atridox(tm) provides a valuable adjunct to periodontal treatment in cases requiring additional care and should be strongly considered for use where the clinical situation so dictates.

Dr. Galler practices in Toronto, Ontario. He is the Co-Director of the Periodontal Plastics Research Centre at the Discipline of Graduate Periodontics, Faculty of Dentistry, University of Toronto.

The author wishes to acknowledge the contributions of Marlo Galler, DDS, University of Western Ontario, in the preparation of this manuscript.

Oral Health welcomes this original article.

REFERENCES

1. Karpinia, K. and I. Magnusson, Recent approaches to periodontal therapy. Expert Opinion on Pharmacotherapy, 2000. 1(6): p. 1219-26.

2. Stein, M., A literature review: oral irrigation therapy. The adjunctive roles for home and professional use. Probe, 1993. 27(1): p. 18-25.

3. Petersilka, G.J., B. Ehmke, and T.F. Flemmig, Antimicrobial effects of mechanical debridement. Periodontology 2000, 2002. 28: p. 56-71.

4. Greenstein, G., Nonsurgical periodontal therapy in 2000: a literature review. Journal of the American Dental Association, 2000. 131(11): p. 1580-92.

5. Walker, P.D. and C. Walker, The supplemental use of antibiotics in periodontal therapy. Journal of Neuroscience Research, 2000. 59(5): p. 624-31.

6. Ranadive, K.S. and K.M. Bhat, Local antimicrobial delivery in periodontal therapy. Indian Journal of Dental Research, 1998. 9(4): p. 124-30.

7. Goodson, J.M., et al., Multicenter evaluation of tetracycline fiber therapy: II. Clinical response. Journal of Periodontal Research, 1991. 26(4): p. 371-9.

8. Goodson, J.M., et al., Multicenter evaluation of tetracycline fiber therapy. III. Microbiological response. Journal of Periodontal Research, 1991. 26(5): p. 440-51.

9. Michalowicz, B.S., et al., Evaluation of periodontal treatments using controlled-release tetracycline fibers: maintenance response. Journal of Periodontology, 1995. 66(8): p. 708-15.

10. Newman, M.G., A 6-month multi-center evaluation of adjunctive tetracycline fiber therapy used in conjunction with scaling and root planing in maintenance patients: clinical results.[see comment].

11. Williams, R.C., et al., Treatment of periodontitis by local administration of minocycline microspheres: a controlled trial. Journal of Periodontology, 2001. 72(11): p. 1535-44.

12. Garrett, S., et al., Two multi-center studies evaluating locally delivered doxycycline hyclate, placebo control, oral hygiene, and scaling and root planing in the treatment of periodontitis. Journal of Periodontology, 1999. 70(5): p. 490-503.

13. Periodontology, T.A.A.o., The role of controlled drug delivery for periodontitis (position paper). Journal of Periodontology, 2000. 71: p. 371-379.

14. Drisko, C.L., et al., Evaluation of periodontal treatments using controlled-release tetracycline fibers: clinical response. Journal of Periodontology, 1995. 66(8): p. 692-9.

15. Pharmaceuticals, C., Atridox product information. 2005.

16. Borden, L., Walker, C, Godowski, K, Prevalence of doxycycline-resistant baceria in an adult periodontitis population. Journal of Dental Research, 1996. 75 (special issue)(153).

17. Borden, L., Walker, C., Stone, C., et al, Microbiota effects following sustained release subgingival delivery of doxycycline. Journal of Dental Research, 1997. 76 (special issue)(153).

18. Johnson, L.R. and N.H. Stoller, Rationale for the use of Atridox therapy for managing periodontal patients. Compendium of Continuing Education in Dentistry, 1999. 20(4 Suppl): p. 19-25; quiz 35.

19. Wennstrom, J.L., et al., Utilisation of locally delivered doxycycline in non-surgical treatment of chronic periodontitis. A comparative multi-centre trial of 2 treatment approaches. Journal of Clinical Periodontology, 2001. 28(8): p. 753-61.

20. Bogle, G., Locally delivered doxycycline hyclate: case selection, preparation, and application. Compendium of Continuing Education in Dentistry, 1999. 20(4 Suppl): p. 26-33; quiz 35.

21. Waerhaug, J., Healing of the dento-epithelial junction following subgingival plaque control. II: As observed on extracted teeth. Journal of Periodontology, 1978. 49(3): p. 119-34.

22. Hirschfeld, L. and B. Wasserman, A long-term survey of tooth loss in 600 treated periodontal patients. Journal of Periodontology, 1978. 49(5): p. 225-37.

23. CollaGenex Pharmaceuticals Announces Publication of Significant New Clinical Data on Periostat, in BusinessWire. 2002.

Photos

FIGURE 1--Moderate interproximal loss of periodontal support between the mandibular left lateral incisor and cuspid (#32 - #33). A decision for conservative treatment was made. The application of Atridox(tm) is of significant benefit in maintaining the periodontal health of the area.
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Caption: FIGURE 1--Moderate interproximal loss of periodontal su...
FIGURE 2--Application of Atridox(tm) three weeks previously resulted an improvement in periodontal health of this area.
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Caption: FIGURE 2--Application of Atridox(tm) three weeks previo...
FIGURE 3--A reactive periodontitis is evident between the mandibular left and right central incisors (#31 - #41) site. Atridox(tm) may serve as a valuable treatment adjunct in maintaining periodontal health in this area.
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Caption: FIGURE 3--A reactive periodontitis is evident between t...
FIGURE 4--A radiograph reveals moderate bone loss of the crestal bone between two implants replacing mandibular central incisors.
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Caption: FIGURE 4--A radiograph reveals moderate bone loss of th...
FIGURE 5--Subgingival application of Atridox(tm) around the implants.
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Caption: FIGURE 5--Subgingival application of Atridox(tm) around...
FIGURE 6--The maxillary left first molar (#26) is periodontally compromised but is an important abutment. Application of Atridox(tm) will assist in stabilizing the periodontal state of this abutment.
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Caption: FIGURE 6--The maxillary left first molar (#26) is perio...
FIGURE 7--The maxillary left first molar (#26) shows radiographic evidence of buccal and mesial furcation involvement.
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Caption: FIGURE 7--The maxillary left first molar (#26) shows ra...
FIGURE 8--Atridox(tm) is dispensed as a unit for clinical delivery.
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Caption: FIGURE 8--Atridox(tm) is dispensed as a unit for clinic...
FIGURE 9--The two syringes are coupled together after removing their caps. The syringes are twisted together to securely lock them. By holding them horizontally, the clear gel is injected into the syringe with doxycycline powder and then the mixed contents of both syringes are pumped back and forth about 100 times to ensure the adequate mixing of the materials.
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FIGURE 10--The cannula may be bent for easy insertion into the periodontal site.
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Caption: FIGURE 10--The cannula may be bent for easy insertion i...
FIGURE 11--The contents of the mixed Doxycycline syringe are inserted into the periodontal site through the blunt cannula.
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FIGURE 12--Atridox material in situ.
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Caption: FIGURE 12--Atridox material in situ.
FIGURE 13--Any excess material may be packed into the periodontal sulcus with a blunted end hand instrument.
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Reader Comments

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Allisa RDH

Hi,
I am a RDH working in Calgary and I am interested in implementing a conjunctive treatment such as Atridox in my office. Where can I find this product for sale in Alberta? Please let me know if there is a rep I can speak too. Thanks!

Posted June 6, 2013 04:08 PM


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