Effects of flurbiprofen on the progression of periodontitis in Macaca mulatta

Abstract

The effect of the nonsteroidal anti‐inflammatory drug flurbiprofen has been studied in the ligature‐induced and spontaneous periodontitis model in the rhesus monkey, Macaca mulatta. Twenty‐four adult monkeys with incipient periodontitis were divided into three disease‐matched groups. Two groups received flurbiprofen at dosages of either 0.27 mg/kg/d or 7.1 mg/kg/d delivered systemically via osmotic minipump. A split‐mouth approach was used, placing ligatures on one side and monitoring the progression of periodontitis at regular intervals for 6 months. Clinical measurements included standardized radiographs, Ramfjord attachment level determinations and assessments of redness, edema and bleeding on probing. There was a statistically significant inhibition of attachment loss (p < 0.05), gingival redness (p < 0.05) and bleeding on probing (p < 0.05) in ligatureinduced and spontaneous periodontitis in the flurbiprofen‐treated animals at 6 months. Eight of 8 ligated control monkeys lost significant attachment (mean loss of 1.06 mm/site). Only 3 of 15 flurbiprofen‐treated ligated monkeys lost any significant attachment, with an overall mean loss of 0.34 mm/site, which was significantly less than the control loss of 1.06 mm/site at p = 4.46 times 10‐3. The odds of a control ligated monkey undergoing significant attachment loss in 6 months are elevated 29.3‐fold, as compared to the flurbiprofen‐treated, cohort monkey group. Flurbiprofen treatment also significantly inhibited spontaneous attachment loss for 6 months as compared to control monkeys, at p < 0.05. These data provide further evidence for the central role of cyclooxygenase products in the progression of periodontal disease. The ability of flurbiprofen to inhibit periodontal attachment loss, even in the presence of gross plaque accumulation, has significant implications for the potential use of flurbiprofen as an adjunctive periodontal therapeutic modality.

The Oral Microbial Consortium's Interaction with the Periodontal Innate Defense System

“…Evidence that these mediators contribute to the characteristic loss of connective tissue and the alveolar bone that surrounds and supports the tooth root associated with periodontal disease comes from studies that demonstrate inflammatory mediator levels decrease after successful treatment (Offenbacher et al ., 1986; Masada et al ., 1990). Further, administration of antiinflammatory drugs that reduce levels of these mediators can suppress bone and tissue destruction (Offenbacher et al ., 1987), and nonsteroidal antiinflammatory drugs that block prostaglandin synthesis can arrest tissue destruction (Offenbacher et al ., 1987). Finally, removal of dental plaque remains the most effective mechanism of restoring an appropriate innate host response in periodontitis patients (Page et al ., 1997), providing more evidence that the bacterial composition associated with periodontitis is directly responsible for a dysfunctional innate host response.…”

Gingival Crevicular Fluid Prostaglandin E2 and Thiobarbituric Acid Reactive Substance Levels in Smokers and Non‐Smokers With Chronic Periodontitis Following Phase I Periodontal Therapy and Adjunctive Use of Flurbiprofen

“…Non‐steroidal anti‐inflammatory drugs (NSAIDs) have been widely researched to modify the host response, and in many studies, it has been demonstrated that NSAIDs reduce the attachment loss in animal and human trials 9‐11 . Some studies 12,13 have demonstrated that the addition of NSAIDs to non‐surgical periodontal treatment can reduce the rate of alveolar bone resorption and gingival inflammation.…”

Inhibition of human periodontal prostaglandin E2 synthesis with selected agents

“…Furthermore, inflamed periodontal tissues which are undergoing attachment loss and bone resorption contain elevated levels of CO products, particularly PGE 2 and to a lesser extent, thromboxane A2 (TxA2) [7][8][9]. Finally, there are considerable data which demonstrate that drugs which block ARA metabolism serve to both diminish the levels of CO products present within the periodontal tissues and inhibit periodontal inflammation, attachment loss and bone resorption [10][11][12][13][14][15][16][17][18][19][20]. It is significant that these drugs can block host-mediated tissue destruction, even in the presence of microbial challenge.…”