"Inflammation's the game, but are the rules always the same?"

While traditional treatments retard and control the majority of periodontal problems, this old story is explained with a new spin: connective tissue and bone loss result from the body's exuberant response to the bacterial plaque. This occurs when the bacterial challenge initiates immune and inflammatory responses. Cells release an assortment of mediators that "stoke" inflammatory fires and recruit additional inflammatory cells to the offended area. Some mediators are familiar; others are not. They include: prostaglandins, matrix metalloproteinases, and cytokines. Once released, these mediators destroy both bone and collagen. So while inflammation is a good thing, i.e. a protective mechanism to isolate and remove bacterial assaults, it can also be destructive when it becomes too enthusiastic.

The importance of this "new" understanding of the inflammatory response is that if we could contain it, we could minimize and perhaps prevent unwanted cell destruction resulting from a periodontal bacterial assault. It turns out that one mediator of collagen destruction can be lowered by exposure to a low (non-antibiotic) dose of doxycycline (which is in the tetracycline family). You have seen it marketed as Periostat (CollaGenex) in television commercials, newsletters, and from reps visiting our offices. Does it work? Should dentists and hygienists be recommending it to all our patients?

To find out, the Journal of the American Dental Association posed a series of questions to two distinguished author/researchers. Their answers considered current research and published articles, and were formulated into a "Point/Counterpoint" format. They evaluated doxycycline use in conjunction with scaling and root planing, pocket reduction, gain of lost tissue (known as attachment gain), drug resistance, clinical indications, cost, and more. They concluded the following:

"The evidence accumulated to date indicates that suppression of the bacterial challenge and subsequent reduction of the host response is the most efficient way to control periodontal disease."

They went on to say that even though doxycycline "might provide some benefit beyond scaling and root planing alone in the treatment of chronic periodontitis…clinicians need to decide if the improvement provided beyond that attained with scaling and root planing alone is clinically meaningful in the management of specific patients." In other words, the authors felt that when standard therapies result in predictable and expected improvements, twice/day doxycycline therapy is not a proven enhancement. It may, however, be useful in cases that do not respond to conventional treatments.

To punctuate these conclusions, another study compared subgingival scaling with and without 20mg twice/day doses of doxycycline. While the group treated with doxycycline did have a statistically lower level of collagenase than the controls (they needed 3 months to achieve these levels), statistically different results were not found in these important categories at 12 weeks:

1. clinical attachment levels;
2. probing depth reduction;
3. bleeding on probing;
4. gingival crevicular flow; and
5. clinical signs of inflammation.

These same parameters were studied at 36 weeks with no major changes in the results. Their conclusion? Interpret the use of doxycycline with caution.**

* Greenstein G. and Lamster I.: Efficacy of subantimicrobial dosing with doxycycline Point/counterpoint JADA 132:457-466, 2001.

** Golub L.M., McNamara T.F., Ryan M.E. et al: Adjunctive treatment with subantimicrobial doses of doxycycline: effects on gingival fluid collagenase activity and attachment loss in adult periodontitis. J Clin Perio 28:146-56, 2001.

New and improved*

Nonsteroidal anti-inflammatory drugs (known as NSAIDs) such as ibuprofen (Motrin and Nuprin), naproxen, diflunisal, and ketoprofen are known to be more effective analgesics than acetaminophen (Tylenol). In addition, many patients find that the NSAIDs are as effective (and sometimes better) than codeine or its derivatives (such as Vicodin or Percocet), but without the possible side effects of nausea and vomiting.

No matter how effective NSAIDs are, they should not be taken by patients who do not tolerate or are allergic to aspirin, or by those patients on anticoagulants. In addition, long-term usage of NSAIDs over weeks and months may cause GI ulcerations, bleeding, or renal toxicity. Not only has impaired renal function been reported with chronic exposure to NSAIDs, but also hospitalization has been required in 0.5-1% of chronic NSAID users.

Now there may be an alternative to the adverse affects of NSAIDs: cyclo-oxygenase-2 inhibitors, more commonly known as COX-2 inhibitors. The two most known (and only ones in the marketplace) are celecoxib (Celebrex) and rofecoxib (Vioxx).

How do NSAIDs and COX-2 inhibitors work? Simply stated, tissue injury provokes an inflammatory response. This inflammation is partially induced by enzymes breaking down damaged cell membranes into their fatty acid components. One common fatty acid, arachidonic acid, is converted by COX enzymes into prostaglandins and other components such as prostacyclins and thromboxanes.

How do NSAIDs and COX-2 inhibitors work? Simply stated, tissue injury provokes an inflammatory response. This inflammation is partially induced by enzymes breaking down damaged cell membranes into their fatty acid components. One common fatty acid, arachidonic acid, is converted by COX enzymes into prostaglandins and other components such as prostacyclins and thromboxanes.

What happens next is fascinating and key to understanding the inflammation/pain mechanism. It turns out that prostaglandins sensitize nerve endings to bradykinins and histamines, both of which are released during the inflammatory response. Prostaglandins also contribute to the vasodilation that produces the redness and swelling of inflammation.

COX enzymes - there are two: COX-1 and COX-2 - synthesize both prostacyclins and thromboxanes, which help maintain healthy gastric mucosa, proper kidney function, and normal platelet activation. COX-1 enzyme is present in tissues at all times. It synthesizes prostanoids that are cytoprotective for normal cell function in the stomach and kidneys, as well as platelet function. COX-2 enzymes are present only in kidneys but are released by other cells following tissue injury. When this occurs, there is a delayed release of COX-2 enzymes by macrophages, monocytes, synovial cells, leukocytes, and fibroblasts. After an injury, it takes 1-3 hours for COX-2 enzymes to appear on the scene.

Now let's put it all together. If a drug blocks both COX-1 and COX-2 enzymes, then it is not only blocking inflammation (mediated by the COX-2 enzymes) but also it is also blocking the cytoprotective mechanisms mediated by the COX-1 enzymes. Aspirin, ibuprofen, naproxen, and ketoprofen block both COX enzymes and for this reason, their prolonged use can possibly damage the GI tract, cause gastric erosions, ulcers, and bleeding. On the other hand, if a drug specifically inhibits the COX-2 enzymes and leaves the COX-1 enzymes intact, it would still produce the desired benefits of pain control (analgesia), temperature control (antipyresis), and anti-inflammation. Enter Vioxx and Celebrex.

The first COX-2 inhibitor approved by the FDA to manage osteoarthritis and rheumatoid arthritis was Celebrex. While this drug is an effective COX-2 inhibitor, studies have shown that it does not give consistent relief for dental pain. A dose of 200 mg. of Celebrex is not as effective as 400 mg of ibuprofen. So while it's a good analgesic for arthritic conditions, it is not as useful for acute post-operative pain.

Vioxx is the second approved COX-2 inhibitor to enter the marketplace. In studies designed to determine which drug is effective in managing pain after third-molar (wisdom teeth) extractions, Vioxx 50 mg was as effective as 400 mg of ibuprofen…and it lasted much longer. In fact, the analgesic benefits of Vioxx 50 mg last 24 hours.

GI problems are far less common with COX-2 inhibitors than with other NSAIDs, but they can occur. Other side effects, including abdominal pain, diarrhea and dyspepsia, have been reported. Chronic use of COX-2 inhibitors can impair kidney function and produce renal toxicity. Aspirin should not be taken with COX-2 inhibitors, and it is important to know that COX-2 inhibitors reduce the elimination of lithium and can also decrease the antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitors such as Lotensin, Vasotec, Monopril, and Zestril.

So in summary, COX-2 inhibitors appear to be just as effective as traditional NSAIDs for post-operative pain control, while reducing the risks for adverse GI toxicity and platelet inhibition. An added benefit is that the pain relief benefits of one dose can last 24 hours. * Moore P.A. and Hersh E.V.: Celecoxib and rofecoxib: The role of COX-2 inhibitors in dental practice. JADA 132:451456, 2001.

But are my bones strong enough?

Everyone with osteoporosis wants to be reassured that they are suitable candidates for dental implants. While many studies have concluded that osteoporosis of the peripheral skeleton does not increase dental implant failure, Friberg et al* conducted a retrospective study on dental implant outcome in patients diagnosed with severe osteoporosis of both the skeleton and the jaws.

Everyone with osteoporosis wants to be reassured that they are suitable candidates for dental implants. While many studies have concluded that osteoporosis of the peripheral skeleton does not increase dental implant failure, Friberg et al* conducted a retrospective study on dental implant outcome in patients diagnosed with severe osteoporosis of both the skeleton and the jaws.

Thirteen patients were studied - 11 female and 2 male - with a mean age of 68 years (ranging from 55-79). Of the 14 jaws treated, 11 were edentulous (six in the maxilla; five in the mandible). Three mandibular jaws were partially edentulous. Seventy (70) implants of various designs and sizes were placed in these osteoporotic jaws while modifying standard surgical techniques. The preparation sites for the implants were under-prepared (the holes were smaller than usual) to insure stability, and conventional healing times were extended to 8.5 months in the maxilla and 4.5 months in the mandible.

Two implants were lost during the study period for a survival rate of 97.1%. Analysis after the implant prostheses were inserted revealed that the remaining implants were stable and functioned in comfort. The authors concluded that dental implants can successfully be placed in patients with generalized osteoporosis with Type IV (the least dense) jaw bones.

* Friber B., Ekestubbe A., Mellström D, and Sennerby L.: Brånemark implants and osteoporosis: a clinical exploratory study. Clin Imp Dent and Related Res 3:50-56, 2001.

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