The U.S. Food and Drug Administration (FDA) has recently approved the use of doxycycline hyclate for the treatment of periodontal disease. Periodontal disease or periodontitis has been reported to afflict 20 to 30 percent of all adults in the industrialized world.  Approximately $6 billion is spent annually to treat periodontal disease.  In the U.S. alone, roughly 67 million adults are believed to be affected.  This prevalence makes periodontal disease one of the most common chronic infectious diseases afflicting adults.  The oral bacteria which cause periodontal disease have been linked to a number of systemic diseases including infective endocarditis, stroke, atherosclerosis and myocardial infarction and preterm low birth weight babies just to name a few (see Systemic Diseases Caused by Oral Microorganisms).

    Doxycycline hyclate was origninally used as a broad spectrum antibiotic.  However, for the treatment of periodontal disease, doxycycline is administered at subantimicrobial doses with absolutely no antibiotic action. The drug is meant to enhance and maintain the benefits of scaling and root planing treatments for periodontal disease as well as to prevent the disease from spreading.  When doxycyclin hyclate is administered at these subantimicrobial doses, the drug acts as to suppress the activity of the enzyme collagenase.  Collagenase belongs to a class of enzymes known as proteases.  Proteases are enzymes which degrade or break down other proteins and enzymes.   Collagenase is the protease which degrades collagen, one of the body's primary connective tissues.  In patients with periodontal disease, the collagen which forms the structural basis of the periodontium is broken down by collagenase.

    Collagenase belongs to a family of enzymes referred to as matrix metalloproteases (see MMPs) which are proteases activated by metal ions.  Elevation in the levels of metalloproteases is believed to account for the majority of the connective tissue destruction which occurs in periodontitis.  Studies have shown that both host cells and invading bacteria produce and secrete collagenase into the periodontal pocket.  Among the body's cells, macrophages, neutrophils (PMNs), fibroblasts, and keratinocytes have all been shown to synthesize and secrete large quantities of collagenase in areas with active periodontal disease.  These cells are believed to be activated by bacterial substances and by proinflammatory cytokines present in the disease. The levels of collagenase in the gingival tissues and in the gingival crevicular fluid (GCF) have been shown to increase almost linearly with the increasing severity of the disease.  Increases in GCF collagenase activity have been shown to positively correlate  with several clinical indexes of periodontal disease including increasing pocket depth, alveolar bone loss, and gingival inflammation. For additional information on the role of proteases, both human and bacterial, in periodontal disease and oral infections see  Proteases in GCF

    Periostat® is the trade name for doxycycline hyclate which is sold in pill form by the company CollaGenex (http://www.collagenex.com).   The Periostat®  capsule contains 20 mg of doxycycline hyclate which is a systemically delivered collagenase inhibitor.  According to CollaGenex, "recent research suggests that periodontitis is best treated by a two-pronged approach: one is reduction of bacterial load in the periodontal pocket and the other is enzyme suppression. Periostat® is the only treatment that suppresses the pathologically elevated levels of tissue-destroying enzymes that may lead to tooth loss in adult periodontitis. And as a systemic therapy, Periostat® treats all periodontal pockets throughout the mouth simultaneously.  The collagenase inhibitor is available as a 20 mg capsules for oral administration indicated as an adjunct to scaling and root planing (SRP) to promote attachment level gains and to reduce probing depths in patients with adult periodontitis.

    Another new FDA approved treatment for periodontitis is called Atridox® developed by Atrix Laboratories, Inc.  (http://www.atrixlabs.com).    Atrix Laboratories develops, manufactures and markets dental and medical products based on its proprietary Atrigel® biodegradeable polymeric technology, which can be used for a broad range of drug deliverey.  Atridox® combines the biodegradeable polymer with a 10% doxycycline hyclate solution.   Atridox® liquid is administered with a syringe and blunt cannula to infected periodontal pocket.  Once administered, Atridox®  fills the periodontal pocket and solidifies.  Doxycyclin is then slowly released at a sustained rate for approximately one week following administration.  According to the manufacturer,  Atridox® does not require an initial treatment of root planing and periodontal scaling and can be used as a stand-alone therapy.   Scaling and root planing are very time-consuming and usually requires the use of a local anesthetic.  

    Another product approved by the FDA for the treatment of periodontal disease is called PerioChip®.  PerioChip®  is a biodegradable chip made of hydrolyzed gelatin impregnated with 2.5 mg of the antibiotic chlorhexidine gluconate.  Chlorhexidine gluconate is a broad-spectrum antibiotic that kills bacteria by destroying the bacterial cell membrane resulting in cell lysis.    Chlorhexidine is released from the PerioChip® in a biphasic manner with 40% being released in the first 24 hours following placement and the remaining 60%  released over the following seven to 10 days. The PerioChip®, a 4 mm x 5 mm x 350 µm chip about the size of a baby's fingernail, is inserted directly into the infected periodontal pocket.  Perichip® is intended to be used as an adjunct to patient periodontal treatment that includes scaling and root planing and good oral hygiene.

For more information on periodontal disease by the people at CollaGenex see http://www.collagenex.com/oralpro/research/periodoa.htm

For more information on the use of Atridox® as well as the use of Atrigel® delivery system see http://atrixlabs.com/prodpipe/atridox_man.htm.   For an interesting article on the link between periodontal disease and other systemic diseases see http://www.atrixlabs.com/pressrels/genco.htm.

For everything you ever wanted know about doxycycline hyclate see the FDA web site information at: http://www.fda.gov/cder/foi/label/1998/50744lbl.pdf.

For additional information on doxycycline hyclate see http://www.dentalbiz.com/Rx/Doxycycline.htm

The home page of Dr. Christian Delnou, Periodontist.  This site provides useful information on Periodontics and Implantology. http://www3.sympatico.ca/cdelnour/cd/english/main.html