Effects of topical applications of meclofenamic acid and ibuprofen on bone loss, subgingival microbiota and gingival PMN response in the primate Macaca fascicularis

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Abstract
Nonsteroidal anti‐inflammatory drugs (NSAIDs) have been shown to alter periodontitis in both animals and humans. This study was initiated in the nonhuman primate (Nhp) model to determine the effect of two NSAIDs on preexisting gingivitis, the conversion of gingivitis to periodontitis, the associated subgingival microbiota, and the gingival PMN response. Eighteen cynomolgus monkeys were divided into three groups and treated on a blind basis with ibuprofen 8%, meclofenamic acid 5%, or placebo applied topically 5 days/ week for 20 wk. After 4 wk of treatment, periodontitis was initiated in one quadrant by the placement of silk ligatures. Clinical parameters, bone loss by densitometric analysis of radiographs (CADIA), and cultural microbiology of subgingival plaque were monitored. In situ PMN chemotaxis was assessed by quantitating the PMNs which entered the sulcus in response to a challenge with n‐formyl‐methionyl‐leucyl‐phenylalanine (FMLP). No significant differences in the clinical parameters were noted by treatment groups. Radiographic bone loss was detected in all experimental sites in placebo animals as compared with 67% and 44% for ibuprofen and meclofenamic acid animals, respectively. Mean CADIA scores/animal showed a significant loss in bone density for placebo at 6 and 16 wk, no change for ibuprofen animals, and a significant increase in density for meclofenamic acid animals. The microbiota of all groups changed with ligation consistent with previous reports of disease initiation in the Nhp. Similar patterns of PMN response to FMLP were elicited in the gingiva of the ibuprofen and placebo groups, with minimal change in PMN levels detected during disease induction: however, sulcular PMNs were significantly higher than placebo in meclofenamic acid animals at all time periods. In this study, ibuprofen inhibited significant bone loss and meclofenamic acid not only inhibited bone loss but produced a significant increase in bone density in the non‐human primate model. These effects were achieved without eliminating clinical gingivitis and without significant effects on the subgingival microbiota. In the meclofenamic acid‐treated animals this was accompanied by a significant increase in PMNs in the local area. Based on this report it appears that topical ibuprofen and meclofenamic acid do not affect the progression of alveolar bone loss equally. In addition, the local increase in PMNs at sites which did not exhibit bone loss may provide insights to the mechanisms involved in the initiation of periodontitis in the cynomolgus monkey.