Tetracycline antibiotics still provide therapeutic benefits for dental patients
Many clinicians recall when subantimicrobial dose doxycycline (SDD) was introduced as an effective adjunct for scaling and root planing in the early 1990s. The idea that a low dose of doxycycline could improve periodontal outcomes, minus antibiotic activity and without the risk of antibiotic resistance, was a completely novel concept. In fact, SDD became known as a host-modulation therapy as a result of enabling the host to respond differently by inhibiting cytokines and matrix metalloproteinases (MMPs), which are notorious for their role in connective tissue destruction.
What should today's clinicians know about using these host-modulating agents?
First, let's review how this subantimicrobial dose of the tetracycline family of antibiotics works to improve clinical results in the treatment of periodontal disease. (But a warning is warranted due to the fact that this topic lends itself to the use of multiple acronyms.) Tetracyclines are a broad-spectrum antibiotic, and a dosage of 100 mg of doxycycline twice daily can be effective in killing a broad range of bacteria. At the subantimicrobial dosage of 20 mg twice daily, doxycycline does not kill or disrupt or really impact bacteria within the biofilm at all; hence the reason an individual can be on a daily dosage of 40 mg and not develop antibiotic resistance to doxycycline.
Much data has been published that supports no antibiotic resistance, even with two years of continuous use at this low dosage. Its "magic" for periodontal patients has to do with its unexpected ability to interfere when a susceptible host produces MMPs in response to the inflammatory process, which in turn breaks down the collagen and leads to hard- and soft-tissue destruction. Introduce SDD to the inflammatory scene and you have an interesting arsenal to help protect against this type of breakdown.
SDD has other powerful attributes in the fight against periodontal breakdown that should interest clinicians looking for ways to alter the host response against the ravages of chronic inflammation. It can significantly reduce the production of inflammatory cytokines, such as interleukin 1, tumor necrosis factor alpha, and markers of alveolar bone resorption, along with mediating other proteinases.
Interestingly, periodontal disease is not the only disease in which host-derived MMPs contribute to the disruption of the collagen matrix. Conditions in this category are referred to as collagenolytic diseases.
Soon after the discovery of how SDD interfered with collagen breakdown in the periodontal condition, the host modulation proved beneficial for patients suffering from chronic inflammatory skin diseases such as acne and rosacea. Oracea is a sustained-release, one-capsule-per-day formulation of doxycycline that has been chemically modified to have zero bacteria-killing properties, and it's widely prescribed for treating rosacea.
Chemically-modified tetracyclines (CMTs) appear to have enhanced anticollagenase properties without antibiotic activity, and are a once daily versus twice daily formulation. Oracea was evaluated in the treatment of periodontal diseases in one double-blind placebo-controlled clinical study and proved to have significant therapeutic potential.1 Additional studies are warranted, but the use of nonantibiotic tetracyclines for periodontal diseases and other systemic diseases is promising.
Due to the crossover between periodontitis and other collagenolytic diseases, future use of SDD or CMTs might prove to be beneficial as a host-modulation therapy for patients suffering from periodontitis and other chronic conditions, such as rheumatoid arthritis, diabetes, osteoporosis, or atherosclerotic cardiovascular diseases.
Because all of these conditions involve the collagen matrix, reducing cytokine and MMP activity could prove clinically relevant for many patients. In fact, there appears to be solid evidence in the role of SDD to profoundly improve outcomes in the management of many chronic inflammatory conditions, according to an article recently published in the International Dental Journal.2
Researchers at Stony Brook University in Stony Brook, New York, have been diligent over the last several years in exploring the connections of host-modulation therapy to reduce MMPs. Some of the studies reveal that nonantimicrobial formulation of doxycycline dramatically reduces C-reactive proteins and various cytokines in the plasma of acute coronary syndrome patients, while simultaneously increasing beneficial HDL cholesterol in atherosclerotic cardiovascular disease (ASCVD) patients with periodontal diseases.
Not surprisingly, these SDD formulations seem to provide significant therapeutic benefit for the management of both periodontitis and ASCVD, especially when accompanied with scaling and root planing to further reduce inflammatory burden.3
For patients suffering from periodontitis in conjunction with other chronic inflammatory conditions, there appears to be a valuable upside and a very low downside to prescribing 20 mg of doxycycline twice daily to interfere with collagen-destroying cytokines and MMPs.
If you found yourself relying on SDD years ago to help manage periodontitis, but lost interest in it or forgot about it, begin identifying patients who will benefit from this host-modulation therapy. Stay tuned to see where the next generation of CMTs leads us. RDH
1. Preshaw PM. Host response modulation in periodontics. Periodontology 2000 2008 48: 92-110.
2. Golub LM, Elburki MS, Walker C, Ryan M, et al. Non-antibacterial tetracycline formulations: host-modulators in the treatment of periodontitis and relevant systemic diseases. International Dental Journal 2016; 66: 127-135.
3. Gu Y, Lee HM, Sorsa T, Salminen A, Ryan M, Slepian MJ, Golub LM. Non-antibacterial tetracyclines modulate mediators of periodontitis and atherosclerotic cardiovascular disease: A mechanistic link between local and systemic inflammation. Pharmacological Research 2011; 64: 573-579.
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