When performing the balancing act of bacteria vs. host resistance, partnering our clinical skills and patients’ home care with Host Modulation Therapy can add weight from our little bag of tricks.
by Diane Brucato-Thomas, RDH, EF, BS
Mesmerizing stage lights flashed off the razor-sharp steel of three machetes flying high and cutting through the air above my son, balanced atop a six-foot unicycle. He wowed the audience by repeatedly catching each of the machetes with expert nimbleness to “Oohs” and “Aahs” from his high school classmates at the annual talent show. A professional juggler who started at age 9, Zach can juggle fire, hatchets, machetes, or any combination you throw at him. I marvel at the fact that he still has all of his digits at age 20 ... or at least he did last time I checked!
Zach once asked me if I wanted to learn how to juggle. I told him that I already knew how - that I, in fact, juggled machetes every day at work! He looked at me suspiciously, but I stood my ground. After all, I wasn’t lying. Matrix metalloproteinases, like collagenase, are little tissue machetes produced by fibroblasts and white blood cells in an effort to move through tissue to reach invading bacteria. Thrown in with the heat of inflammation, I do my best to control them and minimize their potential damage. That is, after all, my job as a periodontal therapist. I even have a partner to juggle with - low-dose doxycycline.
In late 1998, CollaGenex Pharmaceuticals, Inc., launched Periostat™, doxycycline hyclate, a low-dose doxycycline shown to suppress the tissue-destroying activity of collagenase, a proteolytic enzyme - or tissue machete, if you will - overproduced during the body’s immune response to bacterial infection in the periodontal pocket. Collagenase breaks down the supporting structures of the teeth that are made of collagen, including periodontal ligament fibers and collagen fibers within the connective tissue.
Studies show that 20 mg of doxycycline hyclate administered twice daily (recommended to be taken at 12-hour intervals on an empty stomach) acts as an anti-inflammatory agent and inhibits collagenase activity by removing calcium ions that the enzyme requires for stability and activity. This treatment is known as Host Modulation Therapy, or HMT, and is indicated for use as an adjunct to scaling and root planing to promote attachment level gain and to reduce pocket depth in patients with adult periodontitis.
HMT has been recommended especially for periodontal patients who are at high risk for further periodontal breakdown due to systemic complications, such as we see with diabetes or smoking.
In the past, I would pull this treatment from my bag of tricks specifically for high-risk periodontal patients. However, the discovery by Judy Carroll, RDH, a periodontal therapist, of the benefits of starting a patient on low dose doxycycline two weeks prior to conservative periodontal therapy treatment have recently been brought to my attention. This is particularly helpful when conservative periodontal therapy is assisted with dental endoscopy.
Generally, when a periodontal patient presents, periodontal endoscopy reveals a great deal of billowy granulomatous tissue (infected granulation tissue), which engulfs the endoscopic probe, making it difficult to see. Often, this tissue must be curetted away in order to visualize the side of the tooth. However, if a patient is first started on a regime of low-dose doxycycline twice daily for two weeks prior to treatment, the inflammation is greatly reduced, resulting in enhanced visualization. But that’s not all. Reduced inflammation not only means reduced redness and swelling, it also translates to reduced postoperative pain and especially reduced bleeding. This, too, increases visibility with or without endoscopy.
Once a patient has started on low-dose doxycycline as an anti-inflammatory prior to treatment, how long should Host Modulation Therapy continue as an adjunct to periodontal treatment and maintenance? Remember, it inhibits collagenase, which breaks down connective tissue.
Nyman, Lindhe, and Rosling (J of Clin Perio 1977; 4:240) showed that following periodontal surgery, without maintenance, the connective tissue breaks down at a rate of 1 to 2 mm per year. However, if we do nothing, the breakdown rate is 0.1 to 0.3 mm per year. Why is this? New collagen fibers take at least a year to mature, and they break down very easily. The inhibition of collagenase using low-dose doxycycline as HMT allows those new connective tissue fibers an opportunity to mature without constantly being bombarded by tissue machetes.
Some often mistake low-dose doxycycline as an antibiotic and ask, “What about resistant strains?” The practice of people taking doses higher than 20 mg BID for years for the treatment of acne has been happening for decades. Aside from rarely occurring hypergrowth of fungal organisms, taking the tetracyclines in this dose does not appear to have many deleterious effects at all. Much of the damage with respect to creating resistant strains from using tetracycline over time has already happened, because of the treatment of acne and the use of tetracyclines extensively in the animal husbandry industry. So when one looks at the big picture, doxycycline is not as useful an antibiotic as it once was.
According to Dr. Del Rosso, clinical assistant professor in the Department of Dermatology at the University of Nevada School of Medicine: “There’s a dose-related antibiotic effect. In order to reduce bacteria, a given drug must achieve certain inhibitory concentrations to exhibit antibiotic activity. Distinct from their dose-related antibiotic effect, there are a variety of anti-inflammatory mechanisms associated with tetracyclines. However, there is a dosage separation between anti-inflammatory and antibiotic activities that has been identified only with doxycycline.”
So, while doxycycline is a member of the tetracycline class of antibiotics, the dosage of doxycycline achieved when administered at 20 mg twice daily is well below the concentration (150 to 200 mg BID) required to inhibit microorganisms commonly associated with adult periodontitis. Clinical studies of low-dose doxycycline demonstrated no effect on total anaerobic and facultative bacteria in plaque samples from patients administered this dose regimen for nine to 18 months.
Besides the availability of generic low-dose (20 mg) doxycycline, there is now an FDA-approved, single-dose-per-day, 40 mg controlled-release capsule formulation of doxycycline (Oracea™, which stems from the same patent as Periostat™) for the treatment of rosacea in adults. This is specifically referred to as anti-inflammatory dose doxycycline. This dose is anti-inflammatory without antibiotic activity, which reduces any potential issues regarding emergence of antibiotic resistance, especially with long-term administration. A lack of antimicrobial activity has been confirmed based on pharmacokinetic data and microbiologic studies completed over durations of up to 18 months.
Doxycycline is rapidly and nearly completely absorbed after oral administration in the gastrointestinal tract. It is eliminated by renal and fecal excretion of unchanged drug with a half-life of 18 hours. Studies have shown no significant difference in serum half-life of doxycycline in patients with normal and severely impaired renal function.
As with all tetracycline-family drugs, absorption is impaired by antacids containing aluminum, calcium, or magnesium and by iron-containing preparations. Absorption is also impaired by bismuth subsalicylate. As a result, patients should be advised not to take antacids or ingest dairy products in conjunction with low-dose doxcycline.
Since doxycycline is listed as a member of the tetracycline class of antibiotics, which are classified as bacteriostatic, it may interfere with the bactericidal action of members of the ß-lactam (e.g., penicillin) class of antibiotics, so it is not advisable to administer these antibiotics concomitantly. If a patient must be premedicated prophylactically for a dental procedure, he or she should be advised to stop the low-dose doxycycline the day before and resume the day after treatment.
When considering possible side effects, keep in mind that years ago,when original drug tests were run on doxycycline, it was given at antibiotic-level doses. Remember that when these tests are done, if one person has one symptom, it goes down forever on record as a possible side effect. With such a low dose as is being discussed here, side effects are very rare.
Low-dose doxycycline is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines. It is also important to note that tetracyclines have been shown to depress plasma prothrombin activity, so patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage. In addition, concurrent use of tetracyclines may render oral contraceptives less effective.
All things considered, saving teeth is at least as important as treating acne. So when performing the balancing act of bacteria vs. host resistance, partnering our clinical skills and patients’ home care with Host Modulation Therapy (in the form of low-dose doxycycline 20 mg BID) can add weight from our little bag of tricks ... safely controlling those tissue machetes, minimizing their potential damage, and tipping the balance toward host resistance.
About the Author
Diane Brucato-Thomas, RDH, EF, BS, founder of the Hawaii Institute for Wellness in Dentistry, was a periodontal therapist for nearly three decades, and also served as Clinical Specialist for DentalView, Inc.; Anesthesia Examiner for the WREB; Recorder for Hawaii BDE; Advanced Clinical Instructor at Northern Arizona University. Diane is active in ADHA and American Academy of Dental Hygiene, and holds membership in American Association of Dental Examiners and Western Society of Periodontology. Diane was twice awarded “HDHA Outstanding Member” and was first recipient of the “Rosie Wall Community Spirit Grant.” She was also among the first recipients of the Sunstar GUM / RDH Magazine Healthy Gums, Healthy Life Award of Distinction. A speaker and published author, her writings have appeared in the Journal of Practical Hygiene, Chicken Soup for Soul: A Fourth Course and Love is the Best Medicine: for Dental Patients and Dental Teams, for which her short story shared Grand Prize.