The four principal metabolites of cyclooxygenase (CO) were examined during the progression of experimental periodontitis in the rhesus monkey Macaca mulatta. Thirty-two monkeys were divided in four disease-matched groups. Three groups were treated with flurbiprofen, a potent CO inhibitor, at either 0.027, 0.27 or 7.1 mg/kg/day delivered systemically by a subcutaneously-implanted osmotic mini-pump. We have previously described the findings indicating that flurbiprofen treatment significantly retarded clinical attachment loss (ALOSS), redness and radiographic bone loss (BLOSS). This investigation focuses on the changes in CO metabolites which occur during disease progression of ligature-induced periodontitis and on the dose-response relationship of flurbiprofen, as it relates to disease inhibition and the suppression of ARA metabolites within the crevicular fluid (CF). In untreated animals there was a statistically significant 3-fold increase in CF levels of prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) at 3 months, as compared to baseline, which positively correlated with increases in redness, bleeding, ALOSS and BLOSS. CF-PGE2 and TxB2 levels reached a 6-fold peak at 6 months and returned to baseline by 12 months. Flurbiprofen (Fb) prevented the 3-month rise in TxB2, but did not affect the increase in PGE2. At 6 months, Fb administration caused a dose-dependent inhibition of both PGE2 and TxB2. Probit analysis of the dose-response data revealed that the concentration of Fb which caused a 50% inhibition of CF-TxB2 level (the IC50 value for TxB2 synthesis) was approximately two logs lower than the IC50 value for PGE2 synthesis, i.e. TxA2-IC50 = 0.013 vs. PGE2-IC50 = 1.35 mg flurbiprofen/kg/d. The slopes of the PGE2 and TxB2 inhibition curves were identical, consistent with a similar mechanism or singular enzyme for the site of action of Fb inhibition of CO activity. However, the kinetics and sensitivity of Fb inhibition were significantly different for the CO activity responsible for TxB2 and PGE2 synthesis, perhaps due to different compartmentalization of CO within different cell types.

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.

This study examines the microbiota associated with the progression of experimental peri‐implantitis and periodontitis induced concurrently in partially edentulous adult monkeys. Root‐form and plate‐form implants with fixed prosthesis in place for at least 12 months and their corresponding opposite molar teeth were ligated for 6 months. The microbiota in plaque around these ligated dental implants and molars were studied at 0, 1, 2, 3, and 6 months post‐ligation. Plaque samples were analyzed by dark‐field microscopy and selective and non‐selective culture. Putative periodontal pathogens were detected as a major component of the microbiota cultured from plaque samples obtained from experimental peri‐implantitis sites. Overall, the types and relative proportions of putative periodontal pathogens in plaque associated with ligature‐induced peri‐implantitis and ligature‐induced periodontitis were similar. Only levels of anaerobic Actinomyces and spirochetes were significantly different between both sites. Spirochete levels were significantly higher at peri‐implantitis sites when compared with levels at periodontitis sites after 6 months, and spirochete levels increased significantly between 0 and 6 months post‐ligation at implant sites. Levels of spirochetes correlated significantly with probing depth and bone loss at peri‐implantitis sites. Overall, Actinomyces levels were higher at periodontitis sites. Porphyromonas species were not detected continuously as part of the peri‐implantitis microbiota. In conclusion, this study finds that the microbiota associated with the progression of experimental periimplantitis and periodontitis occurring concurrently in partially edentulous mouths are similar. J Periodontol 1998;69:190–194.

Data therefore suggest that membranes left in situ for 1 month or less result in minimal bone gain compared with membranes left in place from 2 to 12 months. In addition, labeling and stained sections clearly showed that the bone produced after 2 months of membrane placement is mature.